Skip to main content
Download PDF

Modifiable risk factors in women at high risk of breast cancer: a systematic review

Breast Cancer Research volume 25, Article number: 45 (2023) Cite this article

Abstract

Background

Modifiable risk factors (alcohol, smoking, obesity, hormone use, and physical activity) affect a woman’s breast cancer (BC) risk. Whether these factors affect BC risk in women with inherited risk (family history, BRCA1/2 mutations, or familial cancer syndrome) remains unclear.

Methods

This review included studies on modifiable risk factors for BC in women with inherited risk. Pre-determined eligibility criteria were used and relevant data were extracted.

Results

The literature search resulted in 93 eligible studies. For women with family history, most studies indicated that modifiable risk factors had no association with BC and some indicated decreased (physical activity) or increased risk (hormonal contraception (HC)/menopausal hormone therapy (MHT), smoking, alcohol). For women with BRCA mutations, most studies reported no association between modifiable risk factors and BC; however, some observed increased (smoking, MHT/HC, body mass index (BMI)/weight) and decreased risk (alcohol, smoking, MHT/HC, BMI/weight, physical activity). However, measurements varied widely among studies, sample sizes were often small, and a limited number of studies existed.

Conclusions

An increasing number of women will recognize their underlying inherited BC risk and seek to modify that risk. Due to heterogeneity and limited power of existing studies, further studies are needed to better understand how modifiable risk factors influence BC risk in women with inherited risk.

Background

A woman’s risk of developing breast cancer is affected significantly by modifiable risk factors, such as alcohol use, smoking, obesity, and physical activity as well as by non-modifiable risk factors, such as BRCA1 or BRCA2 mutations, family history of breast cancer, and familial breast cancer syndromes [1, 2]. With initiatives aimed at increasing awareness of family medical history, such as National Family History Day, a growing number of Americans will become aware of a family history of breast cancer [3]. Moreover, as the availability of genetic tests grows and consumers’ views on genetic testing become more favorable, more women will pursue genetic tests to assess cancer risk [4]. Women with a family history of breast cancer, a familial cancer syndrome, or a confirmed breast cancer-linked genetic variant, may seek to modify their risk in non-surgical and non-medical ways.

Many women who discover a family history or obtain genetic testing results will receive very little accompanying guidance on strategies for non-medical risk reduction. Even for those who receive test results from a healthcare professional, such as a geneticist or genetic counselor, the vast majority of these practitioners do not provide advice on modifiable risk factors related to lifestyle [5].

The primary objective of this review was to assess the association of modifiable risk factors and breast cancer in women at high inherited risk for breast cancer and highlight the salient information that should be readily available to the growing numbers of women aware of their breast cancer risk due to genetic testing or elucidation of family history. This information could thus provide guidance to the many women seeking to reduce their elevated inherited risk of breast cancer.

Methods

This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Search Strategy

For this systematic review, a medical librarian designed and conducted an electronic search using standardized terms and keywords in Ovid Medline, Embase, Scopus, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov. A full search strategy is included in the additional files (Additional file 6) and all searches took place from June to August 2019. Results were exported to EndNote. The automatic duplicate finder in EndNote was used to eliminate duplicates and the results were also manually searched for duplicates. The identified 7885 articles were screened first at the level of title then abstract, language, and type of work for exclusion. The remaining studies were screened by full text for exclusion. This was performed by a single reviewer (S.C.). Exclusion was determined by the below criteria. The reference lists of included articles were searched by hand for additional citations.

Eligibility criteria

Eligible studies included published observational studies, including retrospective and prospective case–control and cohort studies evaluating the association of modifiable risk factors on the development of breast cancer in women with a high non-modifiable risk of developing breast cancer. Modifiable risk factors included weight or body mass index (BMI), smoking, alcohol consumption, physical activity, and hormonal contraception (HC) or menopausal hormone therapy (MHT) use. Eligible studies enrolled adults (≥ 18 years old) and identified participants with a non-modifiable risk factor, defined as, first or second-degree family history of breast cancer (FHBC), BRCA1/2 mutations, or a diagnosed familial cancer syndrome. Only studies published in English were eligible.

Studies were excluded if they did not meet the above eligibility criteria and, additionally, if they did not have a control group that was breast cancer-free and had a positive FHBC, BRCA1/2 mutation, or a familial cancer syndrome. In addition, studies were excluded if data were not reported in strata defined by family history or genetic marker status. Studies that evaluated other non-modifiable risk factors, including specific non-BRCA genetic polymorphisms, or other modifiable risk factors, such as dietary patterns were excluded. In addition, studies were excluded if risk factors were only measured in aggregates, such as the effect of smoking and alcohol but neither individually. Studies involving women that had undergone chemoprevention or prophylactic oophorectomy were excluded. Studies were excluded if they did not use incident breast cancer risk as a primary outcome, including if they measured the outcome of the age of onset of breast cancer. Finally, studies were excluded if only an abstract was available for retrieval.

Quality

Quality was assessed across the body of evidence based on the aspects of quality used by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach (risk of bias, inconsistency, indirectness, imprecision, and publication bias). One reviewer (S.C.) reviewed all papers for their quality based on the GRADE guidelines.

Data extraction and analysis

A data extraction form was developed and used for each study to collect any data (confidence intervals and p values) pertaining to the above-specified modifiable risk factors. Study characteristics, sample size, time to follow-up, subjects’ breast cancer type (ductal carcinoma in situ (DCIS) vs. lobular carcinoma in situ (LCIS) vs. ductal carcinoma (DC) vs. lobular carcinoma (LC)) were also extracted from each paper and recorded on the form. Data and study information were extracted by S.C. and all included studies were reviewed at least twice. Each relevant data point was classified based on the type of risk factor exposure (e.g., current, past, adolescent, etc.) as well as based on whether it indicated a significant increase in risk, decrease in risk, or no association with risk of developing breast cancer.

If a study presented both adjusted and unadjusted data, only the most adjusted data were included. For studies that reported data separately on women with 1st- and 2nd-degree FHBC, only data on women with 1st-degree FHBC were included. Finally, if a study separated women with invasive and in situ breast cancer, only data on women with invasive cancer were included.

The significance of the data was determined by the confidence interval (CI) or the p value, if the CI was not given. For data that included multiple levels of a single modifiable risk factor exposure (e.g., increasing glasses of alcohol per day), the p-trend was used to determine significance, if available. Otherwise, the CI of the highest level was included.

After classifying data based on exposure categories and association with breast cancer risk, if an exposure category contained more than one article (before division by subgroup, e.g., BRCA1 vs. BRCA2) it was included in the corresponding bar chart. If two articles used the same study population and reported data on the same exposure, only the article with the larger sample size was included in the chart.

Results

The literature search (Fig. 1) identified 7885 citations. In total, 7521 articles were excluded by title or abstract leaving 364 articles for full review. The full text of two of these articles could not be obtained. Of the 362 articles reviewed, 95 studies met the inclusion criteria. Four studies were excluded from the review because they reported on the same exposure in the same study population as other included studies but utilized smaller sample sizes. Two additional studies were added based on screening the citations of relevant articles. Thus, a total of 93 studies were included in the systematic review.

Fig. 1
figure 1

Systematic review chart

Full size image

Thirty studies included participants with BRCA1/2 mutations and 3 additional studies included women with BRCA1/2 mutations and women with family history. Ten studies were prospective (Table 1) and 23 were retrospective (Table 2). The 33 studies represented 27 distinct study populations and none of the included studies using the same study population reported on the same risk factor.

Table 1 Characteristics of included studies on BRCA in prospective studies
Full size table
Table 2 Characteristics of included studies on BRCA in retrospective studies
Full size table

Sixty studies included women with a positive family history of breast cancer (FHBC) and 3 additional studies included women with BRCA1/2 mutations and women with FHBC for a total of 63 studies. Twenty-five studies were prospective (Additional file 4: Table S1), and 38 studies were retrospective (Additional file 5: Table S2). The sixty-three studies represented fifty-two study populations. Included studies that used the same study populations investigated different modifiable risk factors or different categories of exposure for the same modifiable risk factor (e.g., alcohol/day vs. lifetime). Of the 12 studies looking at BMI/weight in women with FHBC, 3 studies used the same cohort; of the 32 studies looking at MHT/HC in women with FHBC, 2 pairs and 1 triplet of studies used the same cohorts; and of the 10 studies looking at alcohol in women with FHBC, 2 studies used the same study population.

Six studies investigated the effect of alcohol consumption on breast cancer risk in BRCA 1/2 mutation carriers (Fig. 2A), 10 alcohol consumption in women with FHBC (Fig. 2B), 9 smoking in BRCA 1/2 mutation carriers (Fig. 3A), 9 smoking in women with FHBC (Fig. 3B), 16 hormonal contraception or menopausal hormone therapy in BRCA 1/2 mutation carriers (Additional file 1: Figure S1A and B), 32 hormonal contraception or menopausal hormone therapy in women with FHBC (Additional file 1: Figure S1C), 9 BMI or weight in BRCA 1/2 mutation carriers (Additional file 2: Figure S2A), 12 BMI or weight in women with FHBC (Additional file 2: Figure S2B), 5 physical activity in BRCA 1/2 mutation carriers (Additional file 3: Figure S3A), and 16 physical activity in women with FHBC. Several of these studies included more than one modifiable risk factor.

Fig. 2
figure 2

Alcohol and breast cancer risk in women with BRCA mutations (n = 6) and family history (n = 9). Each bar is divided based on the proportion of included studies that demonstrated an increased risk, decreased risk, or no association with risk of breast cancer due to the specified alcohol exposure. Within each alcohol exposure, each study is represented only once. However, because the category “all alcohol behaviors” combines the results of all other exposure categories, studies may be represented more than once, if the results differ by exposure (e.g., decreased risk with current and no association with total/lifetime alcohol consumption). Numbers on the “all alcohol behaviors” bars indicate the range of risk estimates from studies when reported as a ratio measure (OR/RR/HR). Results from studies reporting only p values or other measures that did not indicate magnitude of effect are not included in these ranges. A Each bar in the figure represents all of the included studies (n = total number of studies) that reported results on the specified alcohol exposure in women with BRCA mutations, separated by BRCA mutation, if provided. Of the studies assessing alcohol type, one looked at wine drinking and the other did not specify the type of alcohol assessed. Please see Tables 1 and 2 for all studies cited. B Each bar in the figure represents all of the included studies (n = total number of studies) that reported results on the specified alcohol exposure in women with family history. Please see Additional file 4: Tables S1 and Additional file 5: Table S2 for all studies cited

Full size image
Fig. 3
figure 3

Smoking and breast cancer risk in women with BRCA mutations (n = 9) and family history (n = 9). Each bar is divided based on the proportion of included studies that demonstrated an increased risk, decreased risk, or no association with risk of breast cancer due to the specified smoking exposure. Within each smoking exposure, each study is represented only once. However, because the category “all smoking behaviors” combines the results of all other exposure categories, studies may be represented more than once, if the results differ by exposure (e.g., increased risk with current smoking and no association with past smoking). Numbers on the “all smoking behaviors” bars indicate the range of risk estimates from studies when reported as a ratio measure (OR/RR/HR). Results from studies reporting only p values or other measures that did not indicate magnitude of effect are not included in these ranges. A Each bar in the figure represents all of the included studies (n = total number of studies) that reported results on the specified smoking exposure in women with BRCA mutations, separated by BRCA mutation, if provided. Please see Tables 1 and 2 for all studies cited. B Each bar in the figure represents all of the included studies (n = total number of studies) that reported results on the specified smoking exposure in women with family history. Please see Additional file 4: Table S1 and Additional file 5: Table S2 for all studies cited

Full size image

Alcohol consumption in women with BRCA 1/2 mutations

Figure 2A includes data on the association between alcohol consumption and breast cancer (BC) in women with BRCA mutations. The data are divided into categories for ever, current, lifetime, age at first alcohol use, current alcohol/day, past alcohol/day, alcohol type, and a combined measure based on these seven exposure categories. Drinks/week was investigated in one study and found to be associated with a decreased risk of BC in women with BRCA1 mutations and no association with BC risk in women with BRCA2 mutations [6]. Of the six studies that looked at alcohol and BC risk, two found that a few of the alcohol exposures investigated decreased risk and the remaining studies found no association with BC risk [6,7,8,9,10,11].

Although the alcohol exposures investigated by each study were organized into a few categories, within those categories there were still multiple definitions of these exposures, as can be seen in Table 3. Ever and current alcohol consumption was defined consistently across studies; however, the other exposures varied.

Table 3 Variations in the definitions of alcohol exposures
Full size table

Alcohol consumption in women with family history of breast cancer

Figure 2B represents data on the impact of alcohol consumption on the development of BC in women with FHBC, divided into categories for past alcohol/day, current alcohol/day, cumulative alcohol, and all alcohol behaviors, a combined measure based on the other three categories. Additional alcohol exposures that appeared in only one article and thus are not presented in Fig. 2B include duration of alcohol use, age at first alcohol consumption, and current alcohol use (with no indication of quantity per day), which all had no association with BC risk as well as current or ever binging, blacking out, or drinking to the point of hurting one’s health, which all increased risk of BC [12, 13]. Overall, all studies demonstrated that alcohol consumption increased or had no association with BC risk (see Additional file 4: Table S1 and Additional file 5: Table S2 and Fig. 2B) [14,15,16,17,18,19,20,21].

Although the alcohol exposures investigated by each study were organized into a few categories, within those categories the definitions of these exposures still vary significantly as illustrated in Table 4. Table 4 demonstrates the various ways the particular alcohol exposure was defined by the studies included.

Table 4 Variations in the definitions of alcohol exposures
Full size table

Cigarette smoking in women with BRCA 1/2 mutations

Figure 3A depicts data on the association of cigarette smoking with BC risk in women with BRCA mutations. Data are separated into exposure categories: ever, current, past, age at smoking initiation, pack-years, and packs/week. Additional exposures that appeared in single studies included total years of smoking, which was associated with increased risk of BC and time since last cigarette use, which found no association with BC [11, 22]. Overall, two studies reported that a few of the smoking exposures were associated with decreased risk of BC and the remaining studies had no association with BC risk [9,10,11,12, 23,24,25,26,27].

Analogous to alcohol exposures, smoking exposure definitions also varied across studies as demonstrated in Table 5. The definitions of ever, current, and past were largely consistent across studies, and the remaining exposure categories varied widely.

Table 5 Variations in the definitions of smoking exposures
Full size table

Cigarette smoking in women with family history of breast cancer

Figure 3B represents data on the association between cigarette smoking and the development of BC in women with FHBC, divided into ever, current, past, age at initiation of, and duration of smoking as well as a combined measure based on the other four categories. One study additionally looked at cigarettes/day and age at first cigarette use and found no association for either with BC risk [28]. All studies reported that smoking increased or had no association with BC risk (see Additional file 4: Tables S1 and Additional file 5: Table S2 and Fig. 3B) [19, 20, 28,29,30,31,32,33,34].

Similar to alcohol exposures, although study findings were organized into categories of smoking exposure, the definitions of some of these exposures remain varied, as shown in Table 6. Ever, current, and past smoking were defined similarly across studies with no specification beyond those labels, whereas duration and age at smoking initiation varied.

Table 6 Variations in the definitions of smoking exposures
Full size table

Menopausal hormone therapy, hormonal contraception, weight, and physical activity

Tables 3, 4, 5, and 6 illustrate the myriad ways that exposure to a modifiable factor was defined in the included studies. Although not featured in a table format, this variability was only greater in the remaining modifiable risk factors (MHT/HC, BMI/weight, and physical activity).

Menopausal hormone therapy and hormonal contraception in women with BRCA 1/2 mutations

Data on the association of MHT/HC with BC risk in women with BRCA mutations are included in Additional file 1: Figures S1A, B. Most studies indicated no association with BC, a few indicated an increased risk for MHT/HC use in women with BRCA1, and a little less than one-third indicated a decreased risk of BC.

Menopausal hormone therapy and hormonal contraception in women with family history of breast cancer

Data on the association of MHT/HC with BC risk in women with FHBC are included in Additional file 1: Figure S1C. Most studies indicated no association with BC, a few indicated an increased risk, and one indicated a decreased risk of BC.

BMI/weight in women with BRCA 1/2 mutations

Data on the association of BMI/weight with BC risk in women with BRCA mutations are included in Additional file 2: Figure S2A. Most studies that looked at the relationship between elevated BMI/weight and pre- or post- menopausal BC showed no association, a few studies reported increased risk, and a few decreased risk.

BMI/weight in women with family history of breast cancer

Data on the association of BMI/weight with BC risk in women with FHBC are included in Additional file 2: Figure S2B. Most studies that looked at the relationship between elevated BMI/weight and pre-menopausal BC showed no association, one reported increased risk and one decreased risk. A little over half of the studies that looked at postmenopausal BC showed an increased risk, two studies showed decreased risk, and the remaining studies showed no association.

Physical activity in women with BRCA 1/2 mutations

Data on the association of physical activity with BC risk in women with BRCA mutations are included in Additional file 3: Figure S3A. All studies that investigated the association between physical activity and BC showed that increased physical activity decreased or had no association with the risk of BC.

Physical Activity in women with family history of breast cancer

Data on the association of physical activity with BC risk in women with FHBC are included in Additional file 3: Figure S3B. All studies that investigated the association between physical activity and BC showed that increased physical activity decreased or had no association with the risk of BC.

Other non-modifiable risk factors

Only one eligible study included participants with a familial cancer syndrome (Li Fraumeni). The study explored the effect of hormonal contraception on breast cancer risk and found that the use of oral contraception had no impact on risk, however, increasing the duration of use increased risk.

Quality

The quality of the studies included in this review was analyzed using the GRADE approach, which includes an assessment of risk of bias, inconsistency, indirectness, imprecision, and publication bias. We also assessed the racial/ethnic distribution of the study populations used in included studies to assess the generalizability of findings (Table 7).

Table 7 Racial/ethnic distribution of study populations used in included studies
Full size table

Risk of bias

Risk of bias in the included studies was assessed based on the consistency of the measurement of exposure and outcome, the adequacy of accounting for confounding variables, and the sufficiency of follow-up.

Exposure was measured very inconsistently across studies of the same modifiable risk factors. Studies differed in whether the exposure was measured in the past, present, or specific periods of life, or based on duration as well as the level of exposure investigated within these time frames. A few studies did not specify exposure, in which case the exposure was classified as ever use. Tables 3, 4, 5, and 6 illustrate the heterogeneity of exposure definitions for smoking and alcohol. Despite the variability demonstrated, smoking and alcohol exposures are defined more consistently across studies than MHT/HC, BMI/weight, or physical activity exposures. Not only were studies of these modifiable risk factors more variable in the way exposures were defined but also more likely to undertake further subgroup divisions. For example, studies of BMI/weight and HC/MHT commonly, but not universally, assessed the impact of menopausal status or utilized postmenopausal (POM) or pre-menopausal (PRM) participants only.

There was less variation in the way studies measured and classified non-modifiable risk factors. Four studies including women with BRCA mutations included women with BRCA1 mutations only. The remaining studies included women with BRCA1 or BRCA2 mutations and studied them combined or separately. Most studies of women with FHBC included women with a 1st-degree relative with BC. Nine studies included women with 1st- or 2nd-degree relatives with BC, one study included only women with a 2nd-degree relative, and six studies did not specify the degree of relatedness of the relative.

The outcome was reported largely consistently across studies as breast cancer. Though many studies did not specify the type of breast cancer (DCIS vs. LCIS vs. invasive) with which their participants were diagnosed, those studies that did, most commonly included participants with invasive breast carcinoma (IBC) and occasionally additionally included DCIS. Two studies used only participants with DCIS. Breast cancer status was collected by self- or proxy-report, physician report, or health records.

Most of the studies included adjusted for at least some of the other known risk factors such as age, age at menarche, menopausal status, age at first birth, parity, as well as those factors included in this review. In those studies that reported follow-up, it ranged from 4 to 26 years with an average of 9.9 years and a median of 7.8 years.

Imprecision

There was significant heterogeneity in exposures measured as discussed above; thus, it would be very difficult to compare confidence intervals directly or to perform a statistical test of heterogeneity.

Indirectness

Most of the studies included directly assessed the question of how modifiable risk factors affect women with non-modifiable risk of BC in the main analysis or as a subgroup analysis. However, small sample sizes in many of the articles likely reduce the generalizability of their findings. Sample sizes in the included studies ranged from 68 to 4,984 women with BRCA mutations and 24 to 43,713 women with FHBC, including both cases and controls. However, when studies investigated specific exposures, such as glasses/day of alcohol, sample sizes could fall as low as 4 participants.

Publication bias

Although it would not be possible to assess publication bias using a funnel plot, it is generally assumed that unpublished studies are mostly small null studies.

Race/ethnicity data

Studies varied in reporting of the information about the racial/ethnic distribution of the study populations used. While some detailed the demographics of participants by race (such as White, Black, etc.), others reported on the numbers of French-Canadian and Jewish participants. There were also a significant number of studies that did not provide any information on race or ethnicity for the study populations used. The studies included in this review represent a wide number of countries with several using international cohorts, though most were conducted in Western countries such as the USA, Canada, Europe, and Australia. Additionally, a few studies represented Asian countries including Japan and Korea. With the lack of detailed and consistent reporting of racial and ethnic demographics of study populations used, it is difficult to assess the generalizability of findings.

Discussion

All women face some risk of breast cancer and modifiable risk factors have been demonstrated to be an important component of that risk [2]. Some risk factors such as low physical activity and alcohol use have shown a consistent pattern of increasing breast cancer risk [35]. Though trends in breast cancer risk related to other risk factors such as hormonal contraception use and body mass index have been linked to breast cancer risk, the relationship differs based on menopausal status and age. Given the smaller numbers of women with BRCA mutations or family history, necessitating further subdivision of subjects by age or menopausal status makes the elucidation of these trends more challenging.

Despite robust research on modifiable risk factors for breast cancer, it has remained unclear how, if at all, modifiable risk factors affect breast cancer risk in women with underlying high risk due to inherited non-modifiable risk factors. Particularly as women become more aware of both their family histories and commonly tested genetic polymorphisms, such as in BRCA1/2, information on modifiable risk factors for high-risk women will become even more critical. It is also important to consider how these modifiable factors affect the risk of other cancers that patients with BRCA1/2 mutations are at increased risk of, such as ovarian cancer [36].

Although this review included ten or more studies with women with positive family history for every investigated modifiable risk factor, fewer were available for most modifiable risk factors in BRCA1/2 mutation carriers, and only one study investigated women with a familial cancer syndrome, despite the search including several familial cancer syndromes. Furthermore, the studies in this review present risk estimates based on disparate exposures to modifiable risk factors and often suffer from low sample sizes and low quality.

The inconsistency in the classification and measurement of exposures to modifiable risk factors limited the direct comparison of studies and made it problematic to perform a meta-analysis as well as to draw conclusions on the high-priority modifiable risk factors for women at high risk of BC. Summarizing across all exposures for each modifiable risk factor, the data support that women at high risk of BC are similarly or less strongly affected by the commonly accepted modifiable risk factors for breast cancer. In studies on women with positive family history, very few studies indicated that physical activity or elevated pre-menopausal BMI/weight increased risk or that HC/MHT, smoking, postmenopausal elevated BMI/weight or alcohol use decreased risk, rather they were null or associated with increased risk. Studies of women with BRCA1/2 mutations demonstrated similar though more varied trends with smaller numbers of studies.

The discrepancies in modifiable risk factor exposure also increased risk of bias, decreasing quality. Quality was adequate in other areas such as indirectness and participant classification; however, imprecision could not be assessed due to heterogeneity. The ability to compare studies would improve if the same definitions of exposures were utilized. Alternatively, it could also be worthwhile to obtain the original participant data and to apply consistent definitions retrospectively to accurately compare cohorts.

Conclusion

With growing awareness of family history and utilization of direct-to-consumer genetic testing, it will become easier to conduct higher-powered studies on this subject. In order for future studies to be more meaningful to women considering lifestyle changes, standardization of the reporting of exposures would be beneficial. Although this review suggests that women with high risk could benefit from following the same guidelines on modifiable risk used for women without underlying risk, such as maintaining an active lifestyle with low levels of tobacco and alcohol use, due to the limitations and heterogeneity of existing literature, women at high risk of breast cancer would benefit from further investigations into these and other modifiable risk factors.

Availability of data and materials

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Abbreviations

BC:

Breast cancer

FHBC:

Family history of breast cancer

HC:

Hormonal contraception

MHT:

Menopausal hormone therapy

BMI:

Body Mass Index

DC:

Ductal carcinoma

LC:

Lobular carcinoma

DCIS:

Ductal carcinoma in situ

LCIS:

Lobular carcinoma in situ

IBC:

Invasive breast cancer

POM:

Post-menopausal

PRM:

Pre-menopausal

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

GRADE:

Grading of Recommendations, Assessment, Development and Evaluation

CI:

Confidence interval

References

  1. Stein CJ, Colditz GA. Modifiable risk factors for cancer. Br J Cancer. 2004;90:299–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Tamimi R. Population attributable risk of modifiable and nonmodifiable breast cancer risk factors in postmenopausal breast cancer. Am J Epidemiol. 2016;184:884–93.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Office of the Associate Director for Science (OADS): Genomics & Precision Health. Knowing is not enough—act on your family health history. Centers for Disease Control and Prevention. 2020. Available from: https://www.cdc.gov/genomics/famhistory/knowing_not_enough.htm

  4. Regalado, Antonio. 2017 was the year consumer DNA testing blew up: More people took genetic ancestry tests last year than in all previous years combined. MIT Technol Rev: Biotechnol. 2018. technologyreview.com/2018/02/12/145676/2017-was-the-year-consumer-dna-testing-blew-up/. Accessed 25 Aug 2019.

  5. Albada A. Does and should breast cancer genetic counselling include lifestyle advice? Fam Cancer. 2014;13:35–44.

    Article  PubMed  Google Scholar 

  6. Dennis J, Ghadirian P, Little J, et al. Alcohol consumption and the risk of breast cancer among BRCA1 and BRCA2 mutation carriers. Breast. 2010;19(6):479–83. https://doi.org/10.1016/j.breast.2010.05.009.

    Article  PubMed  Google Scholar 

  7. McGuire V, John EM, Felberg A, et al. No increased risk of breast cancer associated with alcohol consumption among carriers of BRCA1 and BRCA2 mutations ages <50 years. Cancer Epidemiol Biomark Prev. 2006;15(8):1565–7. https://doi.org/10.1158/1055-9965.EPI-06-0323.

    Article  CAS  PubMed  Google Scholar 

  8. Cybulski C, Lubinski J, Huzarski T, et al. Prospective evaluation of alcohol consumption and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat. 2015. https://doi.org/10.1007/s10549-015-3393-4.

  9. Grill S, Yahiaoui-Doktor M, Dukatz R, et al. Smoking and physical inactivity increase cancer prevalence in BRCA-1 and BRCA-2 mutation carriers: results from a retrospective observational analysis. Arch Gynecol Obstet. 2017;296(6):1135–44. https://doi.org/10.1007/s00404-017-4546-y.

    Article  CAS  PubMed  Google Scholar 

  10. Nkondjock A, Robidoux A, Paredes Y, Narod SA, Ghadirian P. Diet, lifestyle and BRCA-related breast cancer risk among French-Canadians. Breast Cancer Res Treat. 2006;98(3):285–94. https://doi.org/10.1007/s10549-006-9161-8.

    Article  CAS  PubMed  Google Scholar 

  11. Lecarpentier J, Noguès C, Mouret-Fourme E, et al. Variation in breast cancer risk with mutation position, smoking, alcohol, and chest X-ray history, in the French National BRCA1/2 carrier cohort (GENEPSO). Breast Cancer Res Treat. 2011;130(3):927–38. https://doi.org/10.1007/s10549-011-1655-3.

    Article  CAS  PubMed  Google Scholar 

  12. White AJ, DeRoo LA, Weinberg CR, et al. Lifetime alcohol intake, binge drinking behaviors, and breast cancer risk. Am J Epidemiol. 2017;186(5):541–9. https://doi.org/10.1093/aje/kwx118.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Huang XE, Hirose K, Wakai K, et al. Comparison of lifestyle risk factors by family history for gastric, breast, lung and colorectal cancer. Asian Pac J Cancer Prevent: APJCP. 2004;5(4):419–27.

    PubMed  Google Scholar 

  14. Egan KM, Stampfer MJ, Rosner BA, et al. Risk factors for breast cancer in women with a breast cancer family history. Cancer Epidemiol Biomark Prev. 1998;7(5):359–64.

    CAS  PubMed  Google Scholar 

  15. La Vecchia A, Negri E, Parazzini F, et al. Alcohol and breast cancer: update from an Italian case-control study. Eur J Cancer Clin Oncol. 1989;25(12):1711–7. https://doi.org/10.1016/0277-5379(89)90339-8.

    Article  PubMed  Google Scholar 

  16. Vachon CM, Cerhan JR, Vierkant RA, et al. Investigation of an interaction of alcohol intake and family history on breast cancer risk in the Minnesota breast cancer family study. Cancer. 2001;92(2):240–8. https://doi.org/10.1002/1097-0142(20010715)92:2%3c240::AID-CNCR1315%3e3.0.CO;2-I.

    Article  CAS  PubMed  Google Scholar 

  17. Katsouyanni K, Signorello LB, Lagiou P, Egan K, Trichopoulos D. Evidence that adult life risk factors influence the expression of familial propensity to breast cancer. Epidemiol (Cambridge, MA). 1997;8:592–5.

    Article  CAS  Google Scholar 

  18. Kim HJ, Jung S, Eliassen AH, et al. Alcohol consumption and breast cancer risk in younger women according to family history of breast cancer and folate intake. Am J Epidemiol. 2017;186(5):524–31. https://doi.org/10.1093/aje/kwx137.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Nomura SJO, Inoue-Choi M, Lazovich D, et al. WCRF/AICR recommendation adherence and breast cancer incidence among postmenopausal women with and without non-modifiable risk factors. Int J Cancer. 2016;138(11):2602–15. https://doi.org/10.1002/ijc.29994.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Colditz GA, Kaphingst KA, Hankinson SE, et al. Family history and risk of breast cancer: nurses’ health study. Breast Cancer Res Treat. 2012;133(3):1097–104. https://doi.org/10.1007/s10549-012-1985-9.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Colditz GA, Rosner BA, Speizer FE. Risk factors for breast cancer according to family history of breast cancer. J Natl Cancer Inst. 1996;88(6):365–71. https://doi.org/10.1093/jnci/88.6.365.

    Article  CAS  PubMed  Google Scholar 

  22. Ko KP, Kim SJ, Huzarski T, et al. The association between smoking and cancer incidence in BRCA1 and BRCA2 mutation carriers. Int J Cancer. 2018;142(11):2263–72. https://doi.org/10.1002/ijc.31257.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ginsburg OG, Lubinski P, Cybulski J, et al. Smoking and the risk of breast cancer in BRCA1 and BRCA2 carriers: an update. Breast Cancer Res Treat. 2009;114(1):127–135. https://doi.org/10.1007/s10549-008-9977-5.

    Article  CAS  PubMed  Google Scholar 

  24. Whittemore AS, John EM, Felberg A, et al. Smoking and risk of breast cancer in carriers of mutations in BRCA1 or BRCA2 aged less than 50 years. Breast Cancer Res Treat. 2008;109(1):67–75. https://doi.org/10.1007/s10549-007-9621-9.

    Article  CAS  Google Scholar 

  25. Ghadiriani P, Lubinski J, Lynch H, et al. Smoking and the risk of breast cancer among carriers of BRCA mutations. Int J Cancer. 2004;110(3):413–6. https://doi.org/10.1002/ijc.20106.

    Article  CAS  Google Scholar 

  26. Brunet JS, Ghadirian P, Rebbeck TR, et al. Effect of smoking on breast cancer in carriers of mutant BRCA1 or BRCA2 genes. J Natl Cancer Inst. 1998;90(10):761–6.

    Article  CAS  PubMed  Google Scholar 

  27. Gronwald JB, T. Huzarski, T. Cybulski, C. Sun, P. Tulman, A. Narod, S. A. Lubinski, J. Influence of selected lifestyle factors on breast and ovarian cancer risk in BRCA1 mutation carriers from Poland. Breast Cancer Res Treat. 2006;95(2):105–109. https://doi.org/10.1007/s10549-005-9051-5.

    Article  PubMed  Google Scholar 

  28. Jones ME, Schoemaker MJ, Wright LB, et al. Smoking and risk of breast cancer in the Generations Study cohort. Breast Cancer Res. 2017;19(1). https://doi.org/10.1186/s13058-017-0908-4.

  29. Couch FJ, Cerhan JR, Vierkant RA, et al. Cigarette smoking increases risk for breast cancer in high-risk breast cancer families. Cancer Epidemiol Biomark Prev. 2001;10(4):327–32.

    CAS  PubMed  Google Scholar 

  30. Brinton LA, Schairer C, Stanford JL, et al. Cigarette smoking and breast cancer. Am J Epidemiol. 1986;123(4):614–22.

    Article  CAS  PubMed  Google Scholar 

  31. Nyante SJ, Gierach GL, Dallal CM, et al. Cigarette smoking and postmenopausal breast cancer risk in a prospective cohort. Br J Cancer. 2014;110(9):2339–47. https://doi.org/10.1038/bjc.2014.132.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Reynolds P, Hurley S, Goldberg DE, et al. Active smoking household passive smoking, and breast cancer: evidence from the California Teachers Study. J Natl Cancer Inst. 2004;96(1):29–37. https://doi.org/10.1093/jnci/djh002.

    Article  CAS  PubMed  Google Scholar 

  33. Gram IT, Braaten T, Terry PD, et al. Breast cancer risk among women who start smoking as teenagers. Cancer Epidemiol Biomark Prev. 2005;14(1):61–6.

    Article  PubMed  Google Scholar 

  34. Suzuki T, Matsuo K, Wakai K, et al. Effect of familial history and smoking on common cancer risks in Japan. Cancer. 2007;109(10):2116–23. https://doi.org/10.1002/cncr.22685.

    Article  PubMed  Google Scholar 

  35. World Cancer Research Fund International/American Institute for Cancer Research. Diet, Nutrition, Physical Activity and Cancer: a Global Perspective. Summ Third Expert Rep. 2018; Available from: https://www.wcrf.org/sites/default/files/Summary-of-Third-Expert-Report-2018.pdf

  36. Weissman SM, Weiss SM, Newlin AC. Genetic testing by cancer site: ovary. Cancer J Jul-Aug. 2012;18(4):320–7. https://doi.org/10.1097/PPO.0b013e31826246c2.

    Article  Google Scholar 

  37. Kim SJ, Huzarski T, Gronwald J, et al. Prospective evaluation of body size and breast cancer risk among BRCA1 and BRCA2 mutation carriers. Int J Epidemiol. 2018;47(3):987–97. https://doi.org/10.1093/ije/dyy039.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Schrijver LH, Olsson H, Phillips KA, et al. Oral contraceptive use and breast cancer risk: Retrospective and prospective analyses from a BRCA1 and BRCA2 mutation carrier cohort study. Article. JNCI Cancer Spectrum. 2018;2(2)doi:https://doi.org/10.1093/jncics/pky023

  39. Kehm RD, Genkinger JM, MacInnis RJ, et al. Recreational physical activity is associated with reduced breast cancer risk in adult women at high risk for breast cancer: a cohort study of women selected for familial and genetic risk. Cancer Res. 2019. https://doi.org/10.1158/0008-5472.CAN-19-1847.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Lecarpentier J, Noguès C, Mouret-Fourme E, et al. Breast cancer risk associated with estrogen exposure and truncating mutation location in BRCA1/2 carriers. Cancer Epidemiol Biomark Prev. 2015;24(4):698–707. https://doi.org/10.1158/1055-9965.EPI-14-0884.

    Article  CAS  Google Scholar 

  41. Pijpe A, Manders P, Brohet RM, et al. Physical activity and the risk of breast cancer in BRCA1/2 mutation carriers. Breast Cancer Res Treat. 2010;120(1):235–44. https://doi.org/10.1007/s10549-009-0476-0.

    Article  PubMed  Google Scholar 

  42. Qian F, Wang S, Mitchell J, et al. Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: a Mendelian Randomization Study. J Natl Cancer Inst. 2019;111(4):350–64. https://doi.org/10.1093/jnci/djy132.

    Article  CAS  PubMed  Google Scholar 

  43. Brohet RM, Goldgar DE, Easton DF, et al. Oral contraceptives and breast cancer risk in the international BRCA1/2 carrier cohort study: a report from EMBRACE, GENEPSO, GEO-HEBON, and the IBCCS Collaborating Group. J Clin Oncol. 2007;25(25):3831–6. [Comment in: J Clin Oncol. 2007 Nov 20;25(33):5327; author reply 5327–8.

  44. Kotsopoulos J, Huzarski T, Gronwald J, et al. Hormone replacement therapy after menopause and risk of breast cancer in BRCA1 mutation carriers: a case-control study. Breast Cancer Res Treat. 2016;155(2):365–73. https://doi.org/10.1007/s10549-016-3685-3.

    Article  CAS  PubMed  Google Scholar 

  45. Lee E, Ma H, McKean-Cowdin R, et al. Effect of reproductive factors and oral contraceptives on breast cancer risk in BRCA1/2 mutation carriers and noncarriers: results from a population-based study. Cancer Epidemiol Biomark Prevent. 2008;17(11):3170–8. https://doi.org/10.1158/1055-9965.EPI-08-0396.

    Article  CAS  Google Scholar 

  46. Park B, Hopper JL, Win AK, et al. Reproductive factors as risk modifiers of breast cancer in BRCA mutation carriers and high-risk non-carriers. Oncotarget. 2017;8(60):102110–8. https://doi.org/10.18632/oncotarget.22193.

  47. Toss A, Grandi G, Cagnacci A, et al. The impact of reproductive life on breast cancer risk in women with family history or BRCA mutation. Oncotarget 2017;8(6):9144–54. doi:https://doi.org/10.18632/oncotarget.13423.

  48. Eisen A, Lubinski J, Gronwald J, et al. Hormone therapy and the risk of breast cancer in BRCA1 mutation carriers. J Natl Cancer Inst. 2008;100(19):1361–7. https://doi.org/10.1093/jnci/djn313.

  49. Haile RW, Thomas DC, McGuire V, et al. BRCA1 and BRCA2 mutation carriers, oral contraceptive use, and breast cancer before age 50. Cancer Epidemiol Biomark Prev. 2006;15(10):1863–70. https://doi.org/10.1158/1055-9965.EPI-06-0258.

    Article  CAS  Google Scholar 

  50. Heimdal K, Skovlund E, Moller P. Oral contraceptives and risk of familial breast cancer. Cancer Detect Prev. 2002;26(1):23–7.

    Article  CAS  PubMed  Google Scholar 

  51. Kotsopoulos J, Olopade OI, Ghadirian P, et al. Changes in body weight and the risk of breast cancer in BRCA1 and BRCA2mutation carriers. Breast Cancer Res. 2005;7(5). doi:https://doi.org/10.1186/bcr1293

  52. Lammert J, Lubinski J, Gronwald J, et al. Physical activity during adolescence and young adulthood and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat. 2018;169(3):561–71. https://doi.org/10.1007/s10549-018-4694-1.

    Article  CAS  PubMed  Google Scholar 

  53. Manders P, Pijpe A, Hooning MJ, et al. Body weight and risk of breast cancer in BRCA1/2 mutation carriers. Breast Cancer Res Treat. 2011;126(1):193–202. https://doi.org/10.1007/s10549-010-1120-8.

    Article  CAS  PubMed  Google Scholar 

  54. Narod SA, Dube MP, Klijn J, et al. Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2002;94(23):1773–9. https://doi.org/10.1093/jnci/94.23.1773.

    Article  CAS  PubMed  Google Scholar 

  55. Bernholtz S, Laitman Y, Kaufman B, et al. Cancer risk in Jewish BRCA1 and BRCA2 mutation carriers: effects of oral contraceptive use and parental origin of mutation. Breast Cancer Res Treat. 2011;129(2):557–63. https://doi.org/10.1007/s10549-011-1509-z.

    Article  CAS  PubMed  Google Scholar 

  56. Kotsopoulos J, Lubinski J, Moller P, et al. Timing of oral contraceptive use and the risk of breast cancer in BRCA1 mutation carriers. Breast Cancer Res Treat. 2014;143(3):579–86. https://doi.org/10.1007/s10549-013-2823-4.

    Article  CAS  PubMed  Google Scholar 

  57. Grandi G, Toss A, Cagnacci A, et al. Combined hormonal contraceptive use and risk of breast cancer in a population of women with a family history. Clin Breast Cancer. 2018;18(1):e15–24. https://doi.org/10.1016/j.clbc.2017.10.016.

    Article  PubMed  Google Scholar 

  58. Bernstein L, Patel AV, Ursin G, et al. Lifetime recreational exercise activity and breast cancer risk among black women and white women. J Natl Cancer Inst. 2005;97(22):1671–9. https://doi.org/10.1093/jnci/dji374.

    Article  PubMed  Google Scholar 

  59. Gong Z, Hong CC, Bandera EV, et al. Vigorous physical activity and risk of breast cancer in the African American breast cancer epidemiology and risk consortium. Breast Cancer Res Treat. 2016;159(2):347–56. https://doi.org/10.1007/s10549-016-3936-3.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Hirose K, Hamajima N, Takezaki T, et al. Physical exercise reduces risk of breast cancer in Japanese women. Cancer Sci. 2003;94(2):193–9. https://doi.org/10.1111/j.1349-7006.2003.tb01418.x.

    Article  CAS  PubMed  Google Scholar 

  61. Marchbanks PA, McDonald JA, Wilson HG, et al. Oral contraceptives and the risk of breast cancer. N Engl J Med. 2002;346(26):2025–32.

    Article  CAS  PubMed  Google Scholar 

  62. Nichols HB, Trentham-Dietz A, Egan KM, et al. Oral contraceptive use and risk of breast carcinoma in situ. Cancer Epidemiol Biomark Prevent. 2007;16(11):2262–8.

    Article  CAS  Google Scholar 

  63. Patel AV, Press MF, Meeske K, et al. Lifetime recreational exercise activity and risk of breast carcinoma in situ. Cancer. 2003;98(10):2161–9. https://doi.org/10.1002/cncr.11768.

    Article  PubMed  Google Scholar 

  64. Sprague BL, Trentham-Dietz A, Newcomb PA, et al. Lifetime recreational and occupational physical activity and risk of in situ and invasive breast cancer. Cancer Epidemiol Biomark Prev. 2007;16(2):236–43. https://doi.org/10.1158/1055-9965.EPI-06-0713.

    Article  Google Scholar 

  65. Murray PP, Stadel BV, Schlesselman JJ. Oral contraceptive use in women with a family history of breast cancer. Obstet Gynecol. 1989;73(6):977–83.

    CAS  PubMed  Google Scholar 

  66. Newcomb PA, Titus-Ernstoff L, Egan KM, et al. Postmenopausal estrogen and progestin use in relation to breast cancer risk. Cancer Epidemiol Biomark Prev. 2002;11(7):593–600.

    CAS  Google Scholar 

  67. Silvera SAN, Miller AB, Rohan TE. Oral contraceptive use and risk of breast cancer among women with a family history of breast cancer: a prospective cohort study. Cancer Causes Control: CCC. 2005;16(9):1059–63.

    Article  PubMed  Google Scholar 

  68. Bardia A, Vachon CM, Olson JE, et al. Relative weight at age 12 and risk of postmenopausal breast cancer. Cancer Epidemiol Biomark Prev. 2008;17(2):374–8. https://doi.org/10.1158/1055-9965.EPI-07-0389.

    Article  Google Scholar 

  69. Hirose K, Tajima K, Hamajima N, et al. Association of family history and other risk factors with breast cancer risk among Japanese premenopausal and postmenopausal women. Cancer Causes Control. 2001;12(4):349–58. https://doi.org/10.1023/A:1011232602348.

    Article  CAS  PubMed  Google Scholar 

  70. Magnusson C, Colditz G, Rosner B, et al. Association of family history and other risk factors with breast cancer risk (Sweden). Cancer Causes Control. 1998;9(3):259–67. https://doi.org/10.1023/A:1008817018942.

    Article  CAS  PubMed  Google Scholar 

  71. Peplonska B, Lissowska J, Hartman TJ, et al. Adulthood lifetime physical activity and breast cancer. Epidemiology. 2008;19(2):226–36. https://doi.org/10.1097/EDE.0b013e3181633bfb.

    Article  PubMed  Google Scholar 

  72. Swerdlow AJ, De Stavola BL, Floderus B, et al. Risk factors for breast cancer at young ages in twins: an international population-based study. J Natl Cancer Inst. 2002;94(16):1238–46.

    Article  PubMed  Google Scholar 

  73. Ursin G, Tseng CC, Paganini-Hill A, et al. Does menopausal hormone replacement therapy interact with known factors to increase risk of breast cancer? J Clin Oncol. 2002;20(3):699–706. https://doi.org/10.1200/JCO.20.3.699.

    Article  CAS  PubMed  Google Scholar 

  74. Weiderpass E, Braaten T, Magnusson C, et al. A prospective study of body size in different periods of life and risk of premenopausal breast cancer. Cancer Epidemiol Biomark Prev. 2004;13(7):1121–7.

    Article  Google Scholar 

  75. Oral contraceptive use and breast cancer risk in young women: Subgroup analyses. Lancet. 1990;335(8704):1507–09. doi: https://doi.org/10.1016/0140-6736(90)93038-Q

  76. Harris RE, Zang EA, Wynder EL. Oral contraceptives and breast cancer risk: a case-control study. Int J Epidemiol. 1990;19(2):240–6.

    Article  CAS  PubMed  Google Scholar 

  77. Lipnick RJ, Buring JE, Hennekens CH, et al. Oral contraceptives and breast cancer. A prospective cohort study. JAMA. 1986;255(1):58–61.

    Article  CAS  PubMed  Google Scholar 

  78. Olsson H, Bladstrom A, Ingvar C, et al. A population-based cohort study of HRT use and breast cancer in southern Sweden. Br J Cancer. 2001;85(5):674–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Paul C, Skegg DC, Spears GF. Oral contraceptives and risk of breast cancer. Int J Cancer. 1990;46(3):366–73.

    Article  CAS  PubMed  Google Scholar 

  80. Tavani A, Negri E, Franceschi S, et al. Oral contraceptives and breast cancer in northern Italy. Final report from a case-control study. Br J Cancer 1993;68(3):568–71.

  81. Long-term oral contraceptive use and the risk of breast cancer. The centers for disease control cancer and steroid hormone study. J Am Med Assoc. 1983;249(12):1591–95. doi: https://doi.org/10.1001/jama.249.12.1591

  82. Claus EB, Stowe M, Carter D. Oral contraceptives and the risk of ductal breast carcinoma in situ. Breast Cancer Res Treat. 2003;81(2):129–36.

    Article  CAS  PubMed  Google Scholar 

  83. Rohan TE, McMichael AJ. Oral contraceptive agents and breast cancer: a population-based case-control study. Med J Aust. 1988;149(10):520–6.

    Article  CAS  PubMed  Google Scholar 

  84. Lando JF, Heck KE, Brett KM. Hormone replacement therapy and breast cancer risk in a nationally representative cohort. Am J Prev Med. 1999;17(3):176–80. https://doi.org/10.1016/S0749-3797(99)00078-1.

    Article  CAS  PubMed  Google Scholar 

  85. Nomura AM, Kolonel LN, Hirohata T, et al. The association of replacement estrogens with breast cancer. Int J Cancer. 1986;37(1):49–53.

    Article  CAS  PubMed  Google Scholar 

  86. Sellers TA, Mink PJ, Cerhan JR, et al. The role of hormone replacement therapy in the risk for breast cancer and total mortality in women with a family history of breast cancer. Ann Intern Med. 1997;127(11):973–80.

    Article  CAS  PubMed  Google Scholar 

  87. Brinton LA, Williams RR, Hoover RN. Breast cancer risk factors among screening program participants. J Natl Cancer Inst. 1979;62(1):37–44.

    CAS  PubMed  Google Scholar 

  88. Carpenter CL, Ross RK, Paganini-Hill A, et al. Effect of family history, obesity and exercise on breast cancer risk among postmenopausal women. Int J Cancer. 2003;106(1):96–102. https://doi.org/10.1002/ijc.11186.

    Article  CAS  PubMed  Google Scholar 

  89. Cerhan JR, Grabrick DM, Vierkant RA, et al. Interaction of adolescent anthropometric characteristics and family history on breast cancer risk in a historical cohort study of 426 families (USA). Cancer Causes Control. 2004;15(1):1–9. https://doi.org/10.1023/B:CACO.0000016566.30377.4e.

    Article  PubMed  Google Scholar 

  90. Dinger JC, Heinemann LAJ, Möhner S, et al. Breast cancer risk associated with different HRT formulations: a register-based case-control study. BMC Women's Health 2006;6 doi: https://doi.org/10.1186/1472-6874-6-13

  91. Grabrick DM, Hartmann LC, Cerhan JR, et al. Risk of breast cancer with oral contraceptive use in women with a family history of breast cancer. J Am Med Assoc. 2000;284(14):1791–8. https://doi.org/10.1001/jama.284.14.1791.

    Article  CAS  Google Scholar 

  92. Niehoff NM, Nichols HB, Zhao S, et al. Adult physical activity and breast cancer risk in women with a family history of breast cancer. Cancer Epidemiol Biomark Prev. 2019;28(1):51–8. https://doi.org/10.1158/1055-9965.EPI-18-0674.

    Article  Google Scholar 

  93. Peters TM, Schatzkin A, Gierach GL, et al. Physical activity and postmenopausal breast cancer risk in the NIH-AARP diet and health study. Cancer Epidemiol Biomark Prev. 2009;18(1):289–96. https://doi.org/10.1158/1055-9965.EPI-08-0768.

    Article  CAS  Google Scholar 

  94. Sellers TA, Davis J, Cerhan JR, et al. Interaction of waist/hip ratio and family history on the risk of hormone receptor-defined breast cancer in a prospective study of postmenopausal women. Am J Epidemiol. 2002;155(3):225–33. https://doi.org/10.1093/aje/155.3.225.

    Article  PubMed  Google Scholar 

  95. Tehard B, Friedenreich CM, Oppert JM, et al. Effect of physical activity on women at increased risk of breast cancer: results from the E3N cohort study. Cancer Epidemiol Biomark Prev. 2006;15(1):57–64. https://doi.org/10.1158/1055-9965.EPI-05-0603.

    Article  Google Scholar 

  96. Verloop J, Rookus MA, van der Kooy K, et al. Physical activity and breast cancer risk in women aged 20–54 years. J Natl Cancer Inst. 2000;92(2):128–35. https://doi.org/10.1093/jnci/92.2.128.

    Article  CAS  PubMed  Google Scholar 

  97. Brinton LA, Hoover R, Szklo M, et al. Oral contraceptives and breast cancer. Int J Epidemiol. 1982;11(4):316–22.

    Article  CAS  PubMed  Google Scholar 

  98. White E, Malone KE, Weiss NS, et al. Breast cancer among young U.S. women in relation to oral contraceptive use. J Natl Cancer Inst 1994;86(7):505–14.

  99. Ravnihar B, Primic Zakelj M, Kosmelj K, et al. A case-control study of breast cancer in relation to oral contraceptive use in Slovenia. Neoplasma. 1988;35(1):109–21.

    CAS  PubMed  Google Scholar 

  100. Pesch B, Ko Y, Brauch H, et al. Factors modifying the association between hormone-replacement therapy and breast cancer risk. Eur J Epidemiol. 2005;20(8):699–711.

    Article  PubMed  Google Scholar 

Download references

Funding

This research was funded by the Washington University in St. Louis School of Medicine Office of Medical Student Research Summer Research Program. Additional funding was provided by the Breast Cancer Research Foundation (grant 22-028). Neither the Washington University in St. Louis Office of Medical Student Research nor the Breast Cancer Research Foundation influenced the design of this review, the analysis or interpretation of the included studies, or the writing of this manuscript.

Author information

Authors and Affiliations

  1. Washington University in St. Louis School of Medicine, St. Louis, MO, USA

    Sarah Y. Cohen, Carolyn R. Stoll, Akila Anandarajah, Michelle Doering & Graham A. Colditz

Authors
  1. Sarah Y. Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carolyn R. Stoll
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Akila Anandarajah
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michelle Doering
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Graham A. Colditz
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

G.C. and S.C. planned the project. M.D. compiled the database search results. S.C., C.S., and G.C. designed the inclusion and exclusion criteria. S.C. and C.S. determined the steps of data collection. S.C. and A.A. reviewed literature and extracted data. S.C. wrote the manuscript with the assistance of A.A., C.S., and G.C. G.C. supervised this project. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Sarah Y. Cohen.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent to participate

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1

. Contraception/Menopausal Hormone Therapy and Breast Cancer Risk in Women with BRCA Mutations (n=13/n=4) and Family History (n=32). A Demonstrates the relationship between use of hormonal contraception (HC) and BC risk in women with BRCA mutations. Each bar in the figure represents all of the included studies (n = total number of studies) that reported results on the specified HC exposure, separated by BRCA mutation, if provided. Each bar is divided based on the proportion of included studies that demonstrated an increased risk, decreased risk, or no association with risk of breast cancer due to the specified HC exposure. Within each HC exposure, each study is represented only once. However, because the category “all HC use” combines the results of all other exposure categories, studies may be represented more than once, if the results differ by exposure (e.g. increase risk with ever use of HC and no association with use before first full term pregnancy). Numbers on the “all HC use” bars indicate the range of risk estimates from studies when reported as a ratio measure (OR/RR/HR). Results from studies reporting only p-values or other measures that did not indicate magnitude of effect are not included in these ranges. About one third of the data on HC and BC risk indicated increased risk, a small proportion indicated decreased risk and the majority indicated no association with risk of BC. For formulation, all included studies relied on use before and after 1975 as a proxy because HC included higher doses of estrogen prior to 1975. Because all studies reporting on use included data for use before 1975, the exposure was defined in this way. However, one study also reported that use after 1975 increased risk in women with BRCA1 and combined BRCA1/2 mutations and had no association with risk in women with BRCA2 mutations. Another study reported that use after 1975 had no association with risk in women with combined BRCA1/2 mutations. Please see Additional file 4: Table S1 for all studies cited. B Demonstrates the relationship between use of menopausal hormone therapy (MHT) and BC risk in women with BRCA mutations. Each bar in the figure represents all of the included studies (n = total number of studies) that reported results on the specified MHT exposure, separated by BRCA mutation, if provided. Each bar is divided based on the proportion of included studies that demonstrated an increased risk, decreased risk, or no association with risk of breast cancer due to the specified MHT exposure. Within each MHT exposure, each study is represented only once. However, because the category “all MHT use” combines the results of all other exposure categories, studies may be represented more than once, if the results differ by exposure (e.g. decrease risk with ever use of MHT and no association with duration of MHT use). Numbers on the “all MHT use” bars indicate the range of risk estimates from studies when reported as a ratio measure (OR/RR/HR). Results from studies reporting only p-values or other measures that did not indicate magnitude of effect are not included in these ranges. Most of the data included on MHT and BC risk indicated no association and a small proportion demonstrated increased or decreased risk of BC. The two studies that evaluated MHT containing unopposed estrogen were included in the figure (formulation), these studies both additionally found that MHT with estrogen and progesterone had no association with risk of BC. Please see Additional file 4: Table S1 for all studies cited. C Demonstrates the relationship between use of menopausal hormone therapy (MHT) or hormonal contraception (HC) and BC risk in women with family history of BC (FHBC). Each bar in the figure represents all of the included studies (n = total number of studies) that reported results on the specified exposure, separated into MHT and HC. Each bar is divided based on the proportion of included studies that demonstrated an increased risk, decreased risk, or no association with risk of breast cancer due to the specified MHT exposure. Within each MHT or HC exposure, each study is represented only once. However, because the category “all MHT/HC use” combines the results of all other exposure categories, studies may be represented more than once, if the results differ by exposure (e.g. increase risk with ever use of HC and no association with duration of HC use). Numbers on the “all MHT use” bars indicate the range of risk estimates from studies when reported as a ratio measure (OR/RR/HR). Results from studies reporting only p-values or other measures that did not indicate magnitude of effect are not included in these ranges. Most of the included data indicated no association between MHT or HC exposures and BC risk and a small proportion demonstrated increased or decreased risk of BC. Additional exposures reported in only a single study and thus not included in the figure were HC taken before 1975 (higher dose), which showed increased risk and use of estrogen only or combined estrogen and progesterone MHT, which demonstrated no difference in risk. Finally, one study evaluated duration of MHT use during menopause as well as in women greater than 50 years old. Only MHT use during menopause was significant and was included in the figure. Please see Additional file 4: Table S1 for all studies cited.

Additional file 2

. BMI/Weight and Breast Cancer Risk in Women with BRCA Mutations (n=8) and Family History (n=12). A Demonstrates the relationship between body mass index (BMI) or weight and BC risk in women with BRCA mutations. Each bar in the figure represents all of the included studies (n = total number of studies) that reported results on the specified measure of BMI or weight, separated by effect on post-menopausal (POM) or pre-menopausal (PRM) BC, if provided. Each bar is divided based on the proportion of included studies that demonstrated an increased risk, decreased risk, or no association with risk of BC due to the specified BMI or weight measure. Within each BMI or weight category, each study is represented only once. However, because the category “any elevated weight/BMI” combines the results of all other exposure categories, studies may be represented more than once, if the results differ by exposure (e.g. increase risk with current weight and no association with adolescent BMI). Numbers on the “any elevated weight/BMI” bars indicate the range of risk estimates from studies when reported as a ratio measure (OR/RR/HR). Results from studies reporting only p-values or other measures that did not indicate magnitude of effect are not included in these ranges. Approximately half of the data included on BMI or weight and BC risk indicated no association with BC risk and about half demonstrated increased or decreased risk of BC. Because most studies looked at high or gain of BMI or weight, studies reporting on low or loss of BMI or weight were not included in the figure. One study found that low current BMI increased risk of PRM BC in women with BRCA2 mutations and had no association with risk of PRM BC in women with BRCA1 mutations. Another study found that low current weight had no association with risk of PRM BC and another found that weight loss decreased risk of BC in women with BRCA1 and BRCA1/2 combined but had no association with BC in women with BRCA2 mutations. No other studies had different results for BRCA1, BRCA2, or combined BRCA1/2 mutation carriers. Please see Additional file 4: Table S1 for all studies cited. B Demonstrates the relationship between body mass index (BMI) or weight and BC in women with FHBC. Each bar in the figure represents all included studies (n = total number of studies) that reported results on BMI or weight, separated by risk of post-menopausal (POM) or pre-menopausal (PRM) BC. Each bar is divided based on the proportion of included studies that demonstrated increased, decreased, or no association with risk of BC. Within each BMI or weight category, each study is represented only once. However, because the category “any elevated weight/BMI” combines the results of all other exposure categories, studies may be represented more than once, if the results differ by exposure (e.g. increase risk with current weight and no association with adolescent BMI). Numbers on the “any elevated weight/BMI” bars indicate the range of risk estimates from studies when reported as a ratio measure (OR/RR/HR). Results from studies reporting only p-values or other measures that did not indicate magnitude of effect are not included in these ranges. Half of the data included on the effect of BMI or weight on POM BC demonstrated increased risk and half reported no association or decreased risk. All studies of the effect of BMI/weight on PRM BC reported no association. The only study that did not separate POM and PRM BC found that adolescent BMI had no association with risk of BC and adolescent weight increased risk of BC. This study additionally assessed low weight at age 12 years old, which showed no association and weight at age 18 years old, which showed no association with BC. Because most studies looked at high BMI/weight, if studies reported low BMI/weight, those data were not included in the figure. One study found no association between low adolescent BMI and BC. Additional exposures reported in a single study and thus not included in the figure were somatotype at 7 years old, which was not associated with BC risk and waist-to-hip ratio, which was associated with increased risk of POM BC. Please see Additional file 4: Table S1 for all studies cited.

Additional file 3

. Physical Activity and Breast Cancer Risk in Women with BRCA Mutations (n=5) and Family History (n=15). A Demonstrates the relationship between physical activity and BC risk in women with BRCA mutations. Each bar in the figure represents all of the included studies (n = total number of studies) that reported results on the specified measure of physical activity. Each bar is divided based on the proportion of included studies that demonstrated an increased risk, decreased risk, or no association with risk of BC due to the specified physical activity measure. Within each physical activity category, each study is represented only once. However, because the category “all physical activity” combines the results of all other exposure categories, studies may be represented more than once, if the results differ by exposure (e.g. decrease risk with adult physical activity and no association with lifetime physical activity). Numbers on the “all physical activity” bars indicate the range of risk estimates from studies when reported as a ratio measure (OR/RR/HR). Results from studies reporting only p-values or other measures that did not indicate magnitude of effect are not included in these ranges. Most of the data on physical activity indicated no association and about a third demonstrated decreased risk of BC. Additional alcohol exposures that appeared in only one article and thus were not presented in this figure include hours/week, duration, sports activity during adolescence and intensity of activity during adolescence, which all showed no association with BC risk as well as current physical activity, which had no association with BC risk in women with BRCA1 mutations and decreased risk in women with BRCA2 mutations. No other studies had different results for BRCA1 and BRCA2 mutation carriers. Please see Additional file 4: Table S1 for all studies cited. B Demonstrates the relationship between physical activity and BC risk in women with FHBC. Each bar in the figure represents all of the included studies (n = total number of studies) that reported results on the specified measure of physical activity. Each bar is divided based on the proportion of included studies that demonstrated an increased risk, decreased risk, or no association with risk of BC due to the specified physical activity measure. Within each physical activity category, each study is represented only once. However, because the category “all physical activity” combines the results of all other exposure categories, studies may be represented more than once, if the results differ by exposure (e.g. decrease risk with hours/week and no association with intensity). Numbers on the “all physical activity” bars indicate the range of risk estimates from studies when reported as a ratio measure (OR/RR/HR). Results from studies reporting only p-values or other measures that did not indicate magnitude of effect are not included in these ranges. Over half the data included indicated no association between physical activity and BC risk and a little less than half indicated decreased risk of BC. Additional exposures reported in only a single study and thus not included in the figure were adolescent physical activity and physical activity from 22 years old to menopause, which both demonstrated increased risk; physical activity post-menopause, which was not associated with BC risk; and minutes per session, which showed a decrease in risk of BC. Studies reporting on current physical activity cited many different types of current activity, such as outdoor and occupational activities, light household work, and less than 80% sedentary activities. Finally, one study with data on hours/week of physical activity reported on hours/week of vigorous and hours/week of moderate intensity physical activity. Hours/week of vigorous activity demonstrated decreased risk of BC and was included in the figure, whereas, hours/week of moderate activity had no association with BC risk and was not included in the figure. Please see Additional file 4: Table S1 for all studies cited.

Additional file 4

. Characteristics of included prospective studies on family history of breast cancer.

Additional file 5

. Characteristics of included retrospective studies on family history of breast cancer.

Additional file 6

. Full search strategy.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cohen, S.Y., Stoll, C.R., Anandarajah, A. et al. Modifiable risk factors in women at high risk of breast cancer: a systematic review. Breast Cancer Res 25, 45 (2023). https://doi.org/10.1186/s13058-023-01636-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13058-023-01636-1

Breast Cancer Research

ISSN: 1465-542X

Contact us