Cumulative Incidence Of Breast Cancer Research Articles

Abstract PO5-18-02: A Population-Based Analysis of the Impact of Omission of Anthracyclines in the Neoadjuvant Setting on the Risk of Mortality

Abstract Background Most patients with high-risk non-metastatic breast cancer are treated with neoadjuvant chemotherapy (NAC), which includes the administration of anthracyclines. The omission of anthracyclines was shown to be associated with excellent outcomes in selected patients. However, the extent to which anthracyclines are omitted among a population of women treated with NAC and its impact on mortality remain unclear. Objective To investigate the extent to which anthracyclines are omitted among a population of patients with invasive breast cancer treated with NAC and to examine the impact of non-anthracycline NAC on risks of breast cancer-specific and all-cause mortality. Methods We performed a retrospective population-based cohort analysis using patient-level health administrative data. The cohort includes women aged ≥18 years with stage I – III invasive breast cancer diagnosed between January 2012 and December 2020, treated with NAC and surgery. Patients were excluded if they received < 50% of the planned chemotherapy regimen, had bilateral breast cancer and/or a previous malignancy. The exposure of interest was anthracycline versus non-anthracycline NAC regimen. The primary and secondary endpoints were breast cancer-specific mortality and overall (all-cause) mortality. Multivariable Cox proportional hazards models adjusted by propensity score, and clinical/pathologic variables including a measure of comorbidity was performed to examine impact of omission of anthracyclines on outcomes. Cumulative incidence curves were generated to calculate the 5-year cumulative incidence of breast cancer and all-cause mortality for the whole cohort and in subset analyses, stratified by stage and receptor subtype. Results The cohort includes 4,180 women. Median follow was 62 months (IQR 44-85) and median age was 51 years (IQR 43-60). Most patients had low co-morbidities (96.0%), Stage II (44.1%) or Stage III (47.7%) disease, underwent mastectomy (72.6%), had axillary node dissection (64.4%) and received post-operative radiotherapy (88.8%). 279 (6.7%) individuals were treated with a non-anthracycline NAC and 3,901 (93.3 %) received an anthracycline NAC. Women who received non-anthracycline NAC were older (median 62 years vs. 50 years; p< 0.001), more likely to have stage I-II disease (77.0% vs. 51.3%; p< 0.001), and more likely to have triple-negative breast cancer (TNBC) (14.0% vs. 24.4%; p< 0.001) than those who received anthracyclines.On propensity adjusted multivariable analysis, factors associated with an increased risk of BC mortality include Stage III (HR 9.3, 95%CI 4.5 - 19.2, p< 0.0001) or stage II at presentation (HR 2.57 95% CI 1.24, 5.34, p=.01) (ref: stage I) or triple negative subtype (HR 3.7 95% CI 3.03, 4.51, p< .0001) (ref: hormone positive/HER2-). There was no significant difference in the relative risks of BC death (HR 0.8, 95% CI 0.5-1.27) or all-cause mortality (HR 0.85, 95% CI 0.60-1.21) for patients selected for treatment without anthracyclines compared to those treated with anthracyclines.Overall, among individuals selected for treatment without or with anthracycline NAC there was no significant difference in the 5-year cumulative incidence of BC (15.4% vs 10.5%, P=.05) or all-cause mortality (16.4% vs 11.9%, P=.07). However, the 5-year cumulative incidence of BC specific death (31.8% vs 16.5%, p=.03) and 5-year cumulative incidence of all-cause death (31.8% vs. 18.2%, p=.06) was higher among 420 women with HER2+ Stage III breast cancer who received non-anthracycline versus anthracycline-based chemotherapy. No difference was observed for other subgroups. Conclusions The omission of anthracyclines in NAC for individuals with stage III HER2+ breast cancer was associated with higher cumulative risks of breast cancer and all-cause mortality but no difference was observed for other subgroups. Further research is warranted to better understand in whom anthracyclines can be safely omitted. Citation Format: Danilo Giffoni M. M. Mata, Rinku Sutradhar, Matthew Castelo, Lena Nguyen, Danielle Rodin, Ezra Hahn, Omolara Fatiregun, Cindy Fong, Sabina Trebinjac, Andrea Eisen, Lawrence Paszat, Katarzyna Jerzak, Eileen Rakovitch. A Population-Based Analysis of the Impact of Omission of Anthracyclines in the Neoadjuvant Setting on the Risk of Mortality [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-18-02.

Abstract PO2-17-11: Management guidelines for epithelial atypia diagnosed in breast screening, based on an analysis of a large prospective cohort study (Sloane Project)

Abstract Background: Epithelial atypia in the breast is most frequently detected through breast screening. Internationally, guidelines differ between advising diagnostic surgical excision of screen-detected atypia versus vacuum-assisted excision (VAE), often with annual follow up surveillance mammography. Prospective data with detailed follow-up and outcomes for subsequent cancer events is lacking. We evaluated a large prospective cohort of screen-detected atypia (Sloane Project) and an expert consensus meeting to develop management recommendations. Methods: We undertook an observational analysis of women with screen-detected epithelial atypia (Atypical Ductal Hyperplasia (ADH), Flat Epithelial Atypia (FEA), Lobular In Situ Neoplasia (LISN), or mixed atypia) reported to the National Health Service (NHS) Breast Screening Programme (BSP) between 01/04/03 and 20/06/18. We estimated cumulative incidence of invasive cancers per 1000 women within 1 and 2 subsequent screening rounds using cumulative incidence functions and repeated these by women’s age, type of atypia and year of diagnosis. Flexible parametric modelling produced hazard ratios (HR). The results were presented at a consensus meeting with clinical experts, patient representation, national decision-makers and commissioners from the NHS in England. A consensus on management recommendations was reached. Results: Among 3238 women (19088 person-years of follow up) with screen-detected atypia, diagnoses increased from 2010 (n=119) to 2015 (n=502). This coincided with the introduction of digital mammography into English screening centres from 2010 and changes in biopsy technique. A total of 141 invasive breast cancers were detected up to December 2018. Cumulative incidence of invasive breast cancer per 1000 women with atypia (ADH, FEA, LISN or mixed) was 14.2 (95% CI 10.3, 19.1) and 45.0 (36.3, 55.1) at 3- and 6-years post atypia based on 40 and 94 cancers, respectively. Women diagnosed with atypia during 2013-2018 had an invasive cancer detected less frequently within 3 years than women with an atypia diagnosis between 2003-2007 or 2008-2012 (6.0 invasive cancers (3.1, 10.9) per 1000 women in 2013-2018 Vs 24.3 (13.7, 40.1) and 24.6 (14.9, 38.3) in 2003-2007 and 2008-2012), suggesting that atypia diagnosis may increasingly contribute to ‘overdiagnosis’. Cancers detected were similar to the general screening population regarding grade, size and nodal involvement. Ipsilateral and contralateral cancers were detected in equal numbers, supporting the concept that atypia represents a risk factor rather than precursor of invasive cancer in the short term. Results by age and type of atypia did not suggest a need for risk-stratified management. Considering subsequent invasive cancer, VAE appeared to be as safe as diagnostic surgical excision of atypia (HR 0.75 (0.45, 1.25)). The expert consensus considered that increased screening of women with screen-detected atypia over and above routine 3-yearly screening was not beneficial, given the overall low numbers of cancers at three years. This applied to all types of atypia and all women who received digital mammography and diagnosis of atypia on core or vacuum-assisted biopsy followed by VAE within a quality assured NHS BSP. Conclusions: Breast atypia represents a risk factor for invasive cancer and does not necessitate surgical excision. Changes to mammography (digital vs plain film) and biopsy techniques (gauge of needle and use of vacuum-assistance) may lead to detection of atypia which is then ‘over-managed’. Current recommendations for annual mammography for 5 years after a diagnosis of epithelial atypia may be overly cautious. We suggest that women with screen detected atypia should be followed up with routine screening appointments. Citation Format: Karoline Freeman, David Jenkinson, Karen Clements, Matthew Wallis, Sarah E Pinder, Elena Provenzano, Hilary Stobart, Nigel Stallard, Olive Kearins, Nisha Sharma, Abeer Shaaban, Cliona Kirwan, Bridget Hilton, Alastair Thompson, Sian Taylor-Phillips. Management guidelines for epithelial atypia diagnosed in breast screening, based on an analysis of a large prospective cohort study (Sloane Project) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-17-11.

Breast Cancer Incidence After a False-Positive Mammography Result

False-positive mammography results are common. However, long-term outcomes after a false-positive result remain unclear. To examine long-term outcomes after a false-positive mammography result and to investigate whether the association of a false-positive mammography result with cancer differs by baseline characteristics, tumor characteristics, and time since the false-positive result. This population-based, matched cohort study was conducted in Sweden from January 1, 1991, to March 31, 2020. It included 45 213 women who received a first false-positive mammography result between 1991 and 2017 and 452 130 controls matched on age, calendar year of mammography, and screening history (no previous false-positive result). The study also included 1113 women with a false-positive result and 11 130 matched controls with information on mammographic breast density from the Karolinska Mammography Project for Risk Prediction of Breast Cancer study. Statistical analysis was performed from April 2022 to February 2023. A false-positive mammography result. Breast cancer incidence and mortality. The study cohort included 497 343 women (median age, 52 years [IQR, 42-59 years]). The 20-year cumulative incidence of breast cancer was 11.3% (95% CI, 10.7%-11.9%) among women with a false-positive result vs 7.3% (95% CI, 7.2%-7.5%) among those without, with an adjusted hazard ratio (HR) of 1.61 (95% CI, 1.54-1.68). The corresponding HRs were higher among women aged 60 to 75 years at the examination (HR, 2.02; 95% CI, 1.80-2.26) and those with lower mammographic breast density (HR, 4.65; 95% CI, 2.61-8.29). In addition, breast cancer risk was higher for women who underwent a biopsy at the recall (HR, 1.77; 95% CI, 1.63-1.92) than for those without a biopsy (HR, 1.51; 95% CI, 1.43-1.60). Cancers after a false-positive result were more likely to be detected on the ipsilateral side of the false-positive result (HR, 1.92; 95% CI, 1.81-2.04) and were more common during the first 4 years of follow-up (HR, 2.57; 95% CI, 2.33-2.85 during the first 2 years; HR, 1.93; 95% CI, 1.76-2.12 at >2 to 4 years). No statistical difference was found for different tumor characteristics (except for larger tumor size). Furthermore, associated with the increased risk of breast cancer, women with a false-positive result had an 84% higher rate of breast cancer death than those without (HR, 1.84; 95% CI, 1.57-2.15). This study suggests that the risk of developing breast cancer after a false-positive mammography result differs by individual characteristics and follow-up. These findings can be used to develop individualized risk-based breast cancer screening after a false-positive result.

Estimating Breast Cancer Overdiagnosis After Screening Mammography Among Older Women in the United States.

Overdiagnosis is increasingly recognized as a harm of breast cancer screening, particularly for older women. To estimate overdiagnosis associated with breast cancer screening among older women by age. Retrospective cohort study comparing the cumulative incidence of breast cancer among older women who continued screening in the next interval with those who did not. Analyses used competing risk models, stratified by age. Fee-for-service Medicare claims, linked to the SEER (Surveillance, Epidemiology, and End Results) program. Women 70 years and older who had been recently screened. Breast cancer diagnoses and breast cancer death for up to 15 years of follow-up. This study included 54 635 women. Among women aged 70 to 74 years, the adjusted cumulative incidence of breast cancer was 6.1 cases (95% CI, 5.7 to 6.4) per 100 screened women versus 4.2 cases (CI, 3.5 to 5.0) per 100 unscreened women. An estimated 31% of breast cancer among screened women were potentially overdiagnosed. For women aged 75 to 84 years, cumulative incidence was 4.9 (CI, 4.6 to 5.2) per 100 screened women versus 2.6 (CI, 2.2 to 3.0) per 100 unscreened women, with 47% of cases potentially overdiagnosed. For women aged 85 and older, the cumulative incidence was 2.8 (CI, 2.3 to 3.4) among screened women versus 1.3 (CI, 0.9 to 1.9) among those not, with up to 54% overdiagnosis. We did not see statistically significant reductions in breast cancer-specific death associated with screening. This study was designed to estimate overdiagnosis, limiting our ability to draw conclusions on all benefits and harms of screening. Unmeasured differences in risk for breast cancer and differential competing mortality between screened and unscreened women may confound results. Results were sensitive to model specifications and definition of a screening mammogram. Continued breast cancer screening was associated with greater incidence of breast cancer, suggesting overdiagnosis may be common among older women who are diagnosed with breast cancer after screening. Whether harms of overdiagnosis are balanced by benefits and for whom remains an important question. National Cancer Institute.

HPV infection and breast cancer risk: insights from a nationwide population study in Taiwan.

The prevalence of cancer, specifically breast cancer, has raised globally. The etiology of breast cancer has been attributed to age, genetic mutations, reproductive history, hormone therapy, lifestyle factors, and viral infections. The human papillomavirus (HPV) has been one of the most widespread sexually transmitted infection in the United States. The role of HPV in breast oncogenesis was hypothesized before, yet the association remained unclear. In this study, we employed a nationwide population study using centralized patient data managed by the Ministry of Health and Welfare in Taiwan and the Taiwan Cancer Registry database. The breast cancer incidence rates of the 467,454 HPV patients were compared to twice as many non-HPV patients with matching sex and age. Cumulative breast cancer incidence rates were presented by a Kaplan-Meier curve, and the relative risk of breast cancer for HPV and non-HPV patients were calculated using Cox-regression model. Our results indicated a crude hazard ratio (HR) and an adjusted hazard ratio (aHR) of 2.336 and 2.271, respectively, when comparing the risk of breast cancer in the HPV and non-HPV group. The risk of breast cancer was comparable or higher than those of head and neck cancer (aHR=1.595) and cervical cancer (aHR=2.225), which both were found to have causal relationships with HPV. The Kaplan-Meier curve further illustrated a higher cumulative risk across 84 months for HPV patients (p<.0001). Besides HPV, age (p<.0001), insurance providers (p<.001), and comorbidities such as abnormal liver function (aHR=1.191, p=.0069) and hyperlipidemia (aHR=1.218, p=.0002) were found to be correlated with higher risks of breast cancer. A correlation between HPV and breast cancer can be inferred using national health databases. More molecular studies are required to understand the mechanism of the virus-induced oncogenesis of the breast.

Prognostic impact of adjuvant endocrine therapy for estrogen receptor-positive and HER2-negative T1a/bN0M0 breast cancer.

538 Background: Adjuvant endocrine therapy (ET) is the standard of care for Estrogen Receptor (ER)-positive early-stage breast cancer. However, many patients suffer from adverse events associated with ET. The prognosis of patients with T1a/bN0 breast cancer with ER-positive and human epidermal growth factor 2 (HER2)-negative is excellent, and it is not clear whether adjuvant ET should be recommended. Here we evaluate the effect of adjuvant ET for ER-positive and HER2-negative T1a/bN0M0 breast cancer. Methods: This study was a multicenter, retrospective cohort study that evaluated adjuvant ET for patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer. Patients who underwent surgery between 2008 and 2012 in 47 institutions of the Japan Clinical Oncology Group (JCOG) breast cancer group were eligible. We analyzed the cumulative incidence of distant metastasis as primary endpoint using the Gray test model and time to event endpoints (distant disease free survival and overall survival) using log-rank test between patients treated with and without adjuvant ET. We also used Gray test model for the analysis of the cumulative incidence of ipsilateral and contralateral breast cancer. Predictive factors were assessed using the Fine-Gray model and the Cox proportional hazards model. Results: The median follow-up period was 9.2 years. Of 4758 eligible patients (1202 T1a [25.3%] and 3556 T1b [74.7%] diseases), 3991 (83.9%) received adjuvant ET. The 9-year cumulative incidence of distant metastasis was 1.5% with ET and 2.6% without ET (adjusted subdistribution hazard ratio [sHR], 0.54; 95% CI, 0.32-0.93). In the multivariate analysis, the independent risk factors of distant metastasis were no ET, mastectomy, high grade, and lymphatic invasion. The 9-year overall survival was 97.0% and 94.4% (HR, 0.54; 95% CI, 0.38-0.77). Adjuvant ET reduced the incidence of ipsilateral and contralateral breast cancer (9-year rates; 1.1% vs 6.9%; sHR, 0.17; 95% CI 0.11-0.28, and 1.9% vs 5.2%; sHR, 0.33; 95% CI, 0.22-0.49). Conclusions: Adjuvant endocrine therapy significantly reduces distant metastases, however the absolute difference is small for ER-positive and HER2-negative T1a/bN0M0 breast cancer. Furthermore, it reduced ipsilateral and contralateral breast cancer as well. Shared decision making regarding the omission of adjuvant endocrine therapy is crucial, especially in patients with low risk of distant metastasis.

Association between gout and subsequent breast cancer: a retrospective cohort study including 67,598 primary care patients in Germany

PurposeThe aim of this retrospective cohort study was to analyze the cumulative incidence of breast cancer following gout and to investigate the association between gout and subsequent breast cancer in 67,598 primary care patients in Germany.MethodsThis study included adult female patients (≥ 18 years) with an initial diagnosis of gout in 1284 general practices in Germany between January 2005 and December 2020. Individuals without gout were matched to gout patients using propensity score matching based on average yearly consultation frequency during the follow-up period, diabetes, obesity, chronic bronchitis/COPD diagnoses, and diuretic therapy. The 10-year cumulative incidence of breast cancer in the cohorts with and without gout was also studied using Kaplan–Meier curves, which were then compared using the log-rank test. Finally, a univariable Cox regression analysis was conducted to assess the association between gout and breast cancer.ResultsAfter up to 10 years of follow-up, 4.5% of gout and 3.7% of non-gout patients were diagnosed with breast cancer. A Cox regression analysis revealed a significant association between gout and subsequent breast cancer in the total population (HR: 1.17; 95% CI: 1.05–1.31). In the age-stratified analyses, gout was only strongly associated with subsequent breast cancer in the age group ≤ 50 (HR: 1.58; 95% CI: 1.10–2.27), but the association was not significant in women over 50 years old.ConclusionTaken together, the findings of our study provide evidence for the association between gout and subsequent breast cancer diagnosis, particularly in the youngest age group.

Abstract P4-03-31: Lifestyle factors are associated with breast cancer risk in women biopsied for benign breast diseases in China: 10-year results of a multi-center, hospital-based, case-control study

Abstract Objective: Benign breast disease (BBD), especially benign proliferative breast disease (BPBD), is related to increased breast cancer risk. However, few studies have examined whether conventional breast cancer risk factors influence risk of breast cancer among women with BBD. The aim of this study was to evaluate the associations of lifestyle factors with risk of breast cancer among women biopsied for BBD within a multi-center, hospital-based, case-control study in China, in order to provide scientific basis of health guidance for BBD patients and lay the foundation for primary prevention of breast cancer. Methods: A multi-center, hospital-based, case-control study was conducted. Patients with BPBD (n=608) and patients with non-proliferative breast disease (NPBD) (n=366) were collected from 23 hospitals in 11 provinces during April 2012 to April 2013. A face-to-face survey, baseline data and fasting blood was collected with all study subjects. Serum adiponectin levels were assayed using ELISA. After 10 years, the cumulative incidence rate of breast cancer in the two groups was counted through follow-up. Logistic regression analysis was used to obtain the association between specific factors and risk of breast cancer. Results: After 10 years’ follow-up, 388 BPBD and 240 NPBD cases were included in the final analysis (Table 1), of which 16 (4.12%) and 3 (1.25%) developed breast cancer, respectively. The cumulative incidence of breast cancer between the two groups was significant difference (P=0.041). Compared with women in the NPBD group, BPBD group were more likely to be central obesity (with higher waist-to-hip ratio (WHR)) (OR 24.98, 95% CI 1.845-336.203, P=0.015) and less likely to have physical activity (OR 0.626, 95% CI 0.416-0.943, P=0.025) and less often to eat carrots (OR 0.616, 95% CI 0.398-0.953, P=0.030) (Table 2). Subgroup analyze indicated that, physical activity, eat carrots and ham sausage, body weight, BMI, waist circumference and WHR were statistical differences in premenopausal BPBD patients, while only physical activity (OR 0.423, 95% CI 0.269-0.665 P &amp;lt; 0.001) was the independent risk factors. Meanwhile, among the factors of Tea consumption, Glycemia, Body weight, BMI, Waist circumference, WHR and HMW/total adiponectin ratio in postmenopausal group, only HMW/total adiponectin ratio (OR 0.041, 95% CI 0.002-0.820 P=0.037) was statistically significant factor. These stratified multivariate logistic regression analysis results are shown in Table 3. Conclusion: In patients with BBD, physical activity may be the protect factor for breast cancer carcinogenesis in premenopausal women while lower HMW/total adiponectin ratio is a risk factor for postmenopausal women, which can provide direction for primary prevention of breast cancer. Table 1. Pathological types of all subjects. Table 2. The results of multivariate Logistic regression analysis. Table 3. Stratified multivariate Logistic regression analysis by menopause status. Citation Format: Chao Zheng, Dandan Ma, Linfeng Zhao, Maolin Guo, Shude Cui, Fuguo Tian, Zhimin Fan, Cuizhi Geng, Xuchen Cao, Zhenlin Yang, Xiang Wang, Hong Liang, Shu Wang, Hongchuan Jiang, Xuening Duan, Haibo Wang, Guolou Li, Qitang Wang, Jianguo Zhang, Feng Jin, Jinhai Tang, Liang Li, Shi-Guang Zhu, Wenshu Zuo, Fei Wang, Lixiang Yu, Fei Zhou, Yujuan Xiang, Mingming Guo, Yongjiu Wang, Wenzhong Zhou, Shuya Huang, Zhaohui Li, Yajie Zhou, Lijuan Hou, Xinyi Yang, Xuan Zhang, Liyuan Liu, Zhigang Yu. Lifestyle factors are associated with breast cancer risk in women biopsied for benign breast diseases in China: 10-year results of a multi-center, hospital-based, case-control study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-31.

Variation in second breast cancer risk after primary invasive cancer by time since primary cancer diagnosis and estrogen receptor status.

In women with previously treated breast cancer, occurrence and timing of second breast cancers have implications for surveillance. The authors examined the timing of second breast cancers by primary cancer estrogen receptor (ER) status in the Breast Cancer Surveillance Consortium. Women who were diagnosed with American Joint Commission on Cancer stage I-III breast cancer were identified within six Breast Cancer Surveillance Consortium registries from 2000 to 2017. Characteristics collected at primary breast cancer diagnosis included demographics, ER status, and treatment. Second breast cancer events included subsequent ipsilateral or contralateral breast cancers diagnosed >6months after primary diagnosis. The authors examined cumulative incidence and second breast cancer rates by primary cancer ER status during 1-5 versus 6-10years after diagnosis. At 10years, the cumulative second breast cancer incidence was 11.8% (95% confidence interval [CI], 10.7%-13.1%) for women with ER-negative disease and 7.5% (95% CI, 7.0%-8.0%) for those with ER-positive disease. Women with ER-negative cancer had higher second breast cancer rates than those with ER-positive cancer during the first 5 years of follow-up (16.0 per 1000 person-years [PY]; 95% CI, 14.2-17.9 per 1000 PY; vs. 7.8 per 1000 PY; 95% CI, 7.3-8.4 per 1000 PY, respectively). After 5 years, second breast cancer rates were similar for women with ER-negative versus ER-positive breast cancer (12.1 per 1000 PY; 95% CI, 9.9-14.7; vs. 9.3 per 1000 PY; 95% CI, 8.4-10.3 per 1000 PY, respectively). ER-negative primary breast cancers are associated with a higher risk of second breast cancers than ER-positive cancers during the first 5 years after diagnosis. Further study is needed to examine the potential benefit of more intensive surveillance targeting these women in the early postdiagnosis period.

Abstract A003: Risks of ductal carcinoma in situ of the breast associated with pathogenic variants in cancer predisposition genes

Abstract Introduction: The relationship between germline pathogenic variants (PVs) in cancer predisposition genes and ductal carcinoma in situ (DCIS) is not well established. The objective of this study is to determine the risks of DCIS and contralateral breast cancer among women with DCIS associated with germline PVs in cancer predisposition genes. Methods: Associations between pathogenic variants in 11 cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, MSH6, PALB2, RAD51C, and RAD51D) and DCIS were determined in case control analyses of a population-based cohort of 3876 women with DCIS and age-matched unaffected women, and in a clinical cohort of 9887 DCIS cases undergoing clinical genetic testing at Ambry Genetics and unaffected reference controls. The incidence of contralateral breast cancer risk in BRCA1, BRCA2, and PALB2 PV carriers with DCIS was also evaluated in a time-to-event analysis. Results: The mean age at diagnosis of DCIS was 50 years in the clinical testing cohort and 59 years in the population-based cohort. The frequency of PVs in 11 predisposition genes among DCIS cases was 6.9% in the clinical testing cohort and 4.9% in the population-based cohort. PVs in ATM, BRCA1, BRCA2, CHEK2, MSH6, PALB2, and RAD51D were associated with significantly increased risks (Odds Ratio (OR) &amp;gt;2) of DCIS in the clinical testing cohort whereas only PVs in BRCA1, CHEK2, PALB2, and ATM were associated with significantly increased risks of DCIS in the population-based cohort. The cumulative incidence of contralateral breast cancer among BRCA1, BRCA2, and PALB2 PV carriers with DCIS was 11% in 5-years and 20% in 15-years. Conclusions: This study provides new insights into PVs that predispose to DCIS. In addition, it establishes an increased risk of contralateral breast cancer risk among women with DCIS who are carriers of PVs in BRCA1, BRCA2, or PALB2. These findings will guide surveillance and risk reducing strategies in germline PV carriers with DCIS. Citation Format: Huaizhi Huang, Ronan E. Couch, Holly LaDuca, Siddhartha Yadav, Eric C. Polley, Nicholas J. Boddicker, Jie Na, Rohan D. Gnanaolivu, David E. Goldgar, Tina Pesaran, Steven N. Hart, Jill S. Dolinsky, Julie R. Palmer, Lauren Teras, Alpa V. Patel, Kathryn J. Ruddy, Janet E. Olson, Celine M. Vachon, Peter Kraft, Song Yao, Amy Trentham-Dietz, Katherine L. Nathanson, Jeffrey N. Weitzel, Susan M. Domchek, Fergus J. Couch, Chunling Hu. Risks of ductal carcinoma in situ of the breast associated with pathogenic variants in cancer predisposition genes [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr A003.

T064: Doxorubicin exposure and breast cancer risk in adolescent and adult Hodgkin lymphoma survivors

Figure 1: Doxorubicin dose-response plot. Dose-response curve for continuous doxorubicin dose and breast cancer risk, adjusted for age at HL treatment, chest radiotherapy and gonadotoxic treatment. Adjusted HRs for doxorubicin dose categories are added. Background: Female Hodgkin lymphoma (HL) survivors treated with chest radiotherapy at a young age have a strongly increased risk of breast cancer (BC). Recent studies in childhood cancer survivors have shown that doxorubicin may also increase BC risk. So far, the association between doxorubicin and BC risk has not been examined in cancer survivors treated at adolescent/adult ages. Methods: We assessed BC risk in a cohort of 1964 female five year HL survivors, treated at ages 15–50 years in 20 Dutch hospitals between 1975 and 2008. Cumulative BC incidence was estimated in the presence of death as a competing risk. Treatment factors were time-dependently included in the multivariable Cox regression analysis, focusing on the effect of doxorubicin exposure on BC risk. Results: HL survivors were treated at a median age of 27.8 years (interquartile range (IQR) 21.9–35.2 years). After a median follow-up of 18.3 years (IQR 12.9–24.7) years, 200 women had developed invasive BC (n=190) and/or ductal carcinoma in situ (n=49). The 30-year cumulative incidence was 19.4% (95% confidence Interval (CI) 16.6–22.3%). Among patients treated with chemotherapy (n=1113), receipt of doxorubicin-containing chemotherapy increased from 32.6% in 1975–1986 to 84.5% in 1998–2008. In multivariable analysis a cumulative dose of >200 mg/m2 was associated with increased BC risk (HR 1.7; 95% CI 1.1–2.4), compared to patients not treated with doxorubicin. BC risk increased 19% (HR 1.19; 95% CI 1.1–1.3) per additional 100 mg/m2 doxorubicine (ptrend=0.003). Receipt of mantle or axillary field irradiation or gonadotoxic therapy did not modify the association between doxorubicin and BC risk. Among patients who received >200 mg/m2 doxorubicin, the HR was 1.6 (95% CI 1.1–2.5) for patients treated with and 2.0 (95% CI 0.9–4.2) for patients treated without mantle or axillary field irradiation (Pinteraction=0.35). Gonadotoxic treatment (>8.4 g/m2 procarbazine or pelvic irradiation) significantly decreased the risk of BC. Conclusion: This study shows that doxorubicin is associated with an increased BC risk among adolescent and adult HL survivors. Now that radiotherapy doses and volumes have decreased and doxorubicin increasingly forms the backbone of HL treatment, the potential association of doxorubicin with increased BC risk is an important issue.

Surgical Management and Contralateral Breast Cancer Risk in Women with History of Radiation Therapy for Hodgkin Lymphoma: Results from a Population-Based Cohort.

Women with history of chest irradiation for Hodgkin lymphoma are at increased risk of developing bilateral breast cancer, although contralateral breast cancer risk estimates in this population remain undefined. We queried the SEER database for women treated with radiation therapy for Hodgkin lymphoma prior to age 30 years and were diagnosed with a subsequent breast cancer between 1990-2016. Trends in surgical management and the 5- and 10-year cumulative incidence of contralateral breast cancer were evaluated. The cohort included 295 women with a median age of 22 years (range 8-30 years) at Hodgkin lymphoma diagnosis, and 42 years (range 22-65 years) at breast cancer diagnosis. Overall, 263 (89.2%) presented with unilateral breast cancer, while 32 (10.8%) presented with synchronous bilateral breast cancer. Breast-conserving surgery was performed in 17.3% of patients, while mastectomy was performed in 82.7%. In 263 patients presenting with unilateral breast cancer, 50 (19.0%) underwent breast-conserving surgery and 213 (81.0%) underwent mastectomy. Subgroup analysis of mastectomy patients demonstrated a 40.5% bilateral mastectomy rate. The 5-year incidence of contralateral breast cancer in women who underwent unilateral surgery was 9.4% [95% confidence interval (CI), 5.6-15.4%], increasing to 20.2% (95% CI, 13.7-29.2%) at 10-year and 29.9% (95% CI, 20.8-41.9%) at 15-year follow-up. Women with a history of prior chest radiation for Hodgkin lymphoma with a diagnosis of breast cancer have a 10-year contralateral breast cancer risk of 20%. These findings support consideration of contralateral prophylactic mastectomy during surgical decision-making for management of this high-risk patient population.

Breast cancer incidence in patients with BRCA-related advanced ovarian cancer receiving olaparib-based maintenance therapy: A pooled analysis from phase III clinical trials.

5566 Background: As the prognosis of BRCA-related advanced ovarian cancer (AOC) continues to improve thanks to the introduction of targeted therapies like poly ADP-ribose polymerase inhibitors (PARPi) and bevacizumab, the occurrence of second primary tumors, in particular breast cancer (BC), is assumed to be more common. Despite this, data on the incidence of BC in this population are poor and guidelines for BC screening or risk reducing strategies are lacking. Methods: Published data from recent PARPi-based, phase III clinical trials involving germline BRCA mutated AOC were reviewed and analyzed. Only studies in which the incidence of at least one second primary solid tumor was reported were included. Cases of second primary BC cancers were pooled to calculate cumulative incidence according to the median follow-up period for each trial. 95% confidence interval (CI) was considered. Results: Four trials (SOLO1, PAOLA1, SOLO2 and SOLO3) involving 1186 germline BRCA 1-2 mutated AOC patients were included ( BRCA1, n = 816; BRCA2, n = 360; BRCA1 + BRCA2, n = 4; missing, n = 6). In all trials, patients were randomized to receive olaparib +/- bevacizumab (n = 788) versus placebo or standard therapies (n = 398). Median age at diagnosis of AOC was 56 years (range, 29-87). With a follow-up ranging from 3.9 months to 5 years, 16 new cases of BC were recorded, 10 in PARPi-based arms and 6 in control arms. Only two patients had a previous history of BC. The total cumulative incidence of BC was 1.37% (95% CI, 0.77-2.18), while cumulative incidences were 1.26% (95% CI, 0.61-2.31) and 1.51% (95% CI, 0.55-3.25) in PARPi-based arms and control arms, respectively. In a sensitivity analysis excluding the SOLO3 trial with the shortest follow-up, the total cumulative incidence was 1.63% (95% CI, 0.92-2.67). Other 20 cases of second primary solid tumors were registered, including 4 cases of non-small cell lung cancer. Conclusions: Patients with germline BRCA-related AOC receiving PARPi-based maintenance therapy can be reassured about the risk of second primary BC and intensive screening should be avoided at least in early treatment phase. More data with long term follow-up are needed.

Correlation between cumulative mammographic density and age-specific incidence of breast cancer: A biethnic study in Israel.

Women with the most extensive breast density, have a 4- to 6-fold higher cancer risk than women with the lowest density. This cross-sectional study evaluated associations of cumulative mammographic density in two distinct ethnic groups with the respective age-specific breast cancer incidences in the population. The study compared four cohorts of 200 women each aged 35 to 49 and 50 to 74, representing Jewish and Arab ethnicity. Breast density measures were calculated from screening mammograms, using a thresholding software (Cumulus). Breast cancer specific incidence values were obtained from the National Cancer Registry. The percent mammographic density was lower for women aged 50 to 74 than 35 to 49 years, both for Jews: 11.7 vs 23.1 and for Arabs: 11.6 vs 18.3. In contrast, the cumulative density increased with age, from 37.30 to 181.24 in Jews, compared to 21.26 to 108.03 in Arabs. Similar trends in breast cancer incidence rates per 100 000 in the Israeli population were apparent, with an increase from 92.95 to 381.91 in Jews, compared to 48.6 to 244.44 in Arabs. Comparing cumulative density of the cohort with respective age-specific breast cancer incidence in the population yielded a highly significant correlation: Jews; r=.97, P < .0001 and Arabs: r=.86, P=.007. A strong association was found between the log of cumulative density and the log of cancer incidence, as well. Our study identified correlations between cumulative mammographic density and breast cancer incidence in two distinct populations. The findings should prompt research to enhance our understanding of the pathogenesis of breast cancer, and lead to novel insights into measures of prevention.

Abstract P3-03-21: Contralateral breast cancers detected by pre-operative MRI in patients diagnosed with DCIS: Whart do they mean?

Abstract Background: For patients with ductal carcinoma in situ (DCIS), data about contralateral breast cancers detected by MRI at primary diagnosis and the impact of MRI use on the incidence and stage of contralateral breast cancers during follow-up are scarce. Methods: We selected all women diagnosed with a primary DCIS in the Netherlands in 2011-2015 from the Netherlands Cancer Registry. The synchronous and metachronous detection of contralateral DCIS and contralateral invasive breast cancer was assessed for patients who did receive an MRI upon primary diagnosis (MRI group) and for an age-matched control group without MRI. Incidence of contralateral disease during follow-up was calculated using competing risk methods.Results: Of the 8486 patients diagnosed with primary DCIS, 1571 (19%) received an MRI. In the MRI group, 0.8% of patients were diagnosed with a synchronous contralateral DCIS and 1.3% with synchronous contralateral invasive breast cancer. Median follow-up time was 6.4 years (IQR: 5.1-7.6). The estimated five-year cumulative incidence of synchronous plus metachronous contralateral DCIS was 2.0% (95% CI: 1.4%-2.8%)) for the MRI group and 0.9% (95% CI: 0.5%-1.5%) for the age-matched control group. The five-year cumulative incidence of contralateral invasive breast cancer was 3.5% (95% CI: 2.7%-4.5%) for the MRI group and 2.3% (95% CI: 1.6%-3.1%) for the age-matched control group. In patients aged &amp;lt;50 years, the cumulative incidence of metachronous contralateral DCIS was statistically significantly higher in the MRI group than in the age-matched controls (sHR= 4.22 (95%CI: 1.19-14.99), P=0.03). This was not the case in patients aged 50-74 years (sHR=0.89 (95%CI: 0.41-1.93), P=0.77). Conclusions: MRI led to more frequent detection of synchronous contralateral invasive breast cancers without lowering the number of metachronous contralateral invasive breast cancers. In patients aged below 50 years, MRI added to conventional imaging led to a persisting higher rate of DCIS diagnosed in the opposite breast, also without influencing the occurrence of invasive breast cancers being detected during the first five years of follow-up. Footnotes Citation Format: Kristien Keymeulen, Sandra Geurts, Loes Kooreman, Lucien Duijm, Sanne Engelen, Sigrid Vanwetswinkel, Ernest Luiten, Sabine Siesling, Adri Voogd, Vivianne Tjan-Heijnen. Contralateral breast cancers detected by pre-operative MRI in patients diagnosed with DCIS: Whart do they mean? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-03-21.

Abstract PD7-07: Surgical management and contralateral breast cancer risk in women with a history of radiation therapy for Hodgkin lymphoma: Results from a population-based cohort

Abstract Background: Women with a history of chest radiation for Hodgkin lymphoma are at an increased risk of developing breast cancer. Although mastectomy has historically been recommended for surgical treatment of breast cancers in women with prior radiation exposure, surgical management trends and contralateral breast cancer risk in this population remain undefined. Methods: We performed a population-based retrospective study using the Surveillance, Epidemiology, and End Results (SEER) database from 1990-2016. Our cohort included women who received radiation for Hodgkin lymphoma prior to 30 years old and were diagnosed with a subsequent breast cancer. We evaluated trends in local therapy including rates of breast conserving surgery (BCS) and mastectomy. In those undergoing unilateral surgery, the Kaplan-Meier method was used to estimate the 5- and 10-year cumulative incidence of contralateral breast cancer. Results: Our final cohort included 295 women with a median age of 22 years (range, 8-30 years) at Hodgkin lymphoma diagnosis, and 42 years (range, 22-65 years) at breast cancer diagnosis. Of these patients, 263 (89.2%) presented with unilateral breast cancer, while 32 (10.8%) presented with synchronous bilateral breast cancer. Overall, BCS was performed in 17.3% of patients and mastectomy was performed in 82.7%. In the 263 patients presenting with unilateral breast cancer, 50 (19.0%) underwent BCS and 213 (81.0%) underwent mastectomy. Subgroup analysis of mastectomy patients with surgical laterality information available demonstrated a 40.5% bilateral mastectomy rate. In the entire cohort, the 5-year incidence of contralateral breast cancer in women who underwent unilateral surgery was 9.4% (95% CI, 5.6-15.4), increasing to 20.2% (95% CI, 13.7-29.2) at 10-years of follow up. Hormone receptor status of the index breast cancer was not associated with significant differences in the incidence of contralateral breast cancer (p=0.13). Conclusions: Women with a history of prior chest radiation for Hodgkin Lymphoma with a diagnosis with breast cancer have a 10-year contralateral breast cancer risk of 20%. These findings support consideration of contralateral prophylactic mastectomy during surgical decision-making in this high-risk patient population. Citation Format: Elisheva R Eisenberg, Anna Weiss, Ipshita Prakash, Sonia Skamene, Mark Basik, Jean Francois Boileau, Lissa Ajjamada, Michael Pollak, Stephanie M Wong. Surgical management and contralateral breast cancer risk in women with a history of radiation therapy for Hodgkin lymphoma: Results from a population-based cohort [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD7-07.

The Relationship Between Breast Density Change During Menopause and the Risk of Breast Cancer in Korean Women.

The aim of this study was to investigate the relationship between changes in breast density during menopause and breast cancer risk. This study was a retrospective, longitudinal cohort study for women over 30 years of age who had undergone breast mammography serially at baseline and postmenopause during regular health checkups at Samsung Medical Center. None of the participants had been diagnosed with breast cancer at baseline. Mammographic breast density was measured using the American College of Radiology Breast Imaging Reporting and Data System. During 18,615 person-years of follow-up (median follow-up 4.8 years; interquartile range 2.8-7.5 years), 45 participants were diagnosed with breast cancer. The prevalence of dense breasts was higher in those who were younger, underweight, had low parity or using contraceptives. The cumulative incidence of breast cancer increased 4 years after menopause in participants, and the consistently extremely dense group had a significantly higher cumulative incidence (CI) of breast cancer compared with other groups [CI of extremely dense vs. others (incidence rate per 100,000 person-years): 375 vs. 203, P < 0.01]. Korean women whose breast density was extremely dense before menopause and who maintained this density after menopause were at two-fold greater risk of breast cancer. Extremely dense breast density that is maintained persistently from premenopause to postmenopause increases risk of breast cancer two fold in Korean women. Therefore, women having risk factors should receive mammography frequently and if persistently extremely dense breast had been detected, additional modalities of BC screening could be considered.

Association of Breast Density With Breast Cancer Risk Among Women Aged 65 Years or Older by Age Group and Body Mass Index

Breast density is associated with breast cancer risk in women aged 40 to 65 years, but there is limited evidence of its association with risk of breast cancer among women aged 65 years or older. To compare the association between breast density and risk of invasive breast cancer among women aged 65 to 74 years vs women aged 75 years or older and to evaluate whether the association is modified by body mass index (BMI). This prospective cohort study used data from the Breast Cancer Surveillance Consortium from January 1, 1996, to December 31, 2012, for US women aged 65 years or older who underwent screening mammography. Data were analyzed from January 1, 2018, to December 31, 2020. Breast Imaging Reporting and Data System breast density category, age, and BMI. The 5-year cumulative incidence of invasive breast cancer by level of breast density (almost entirely fat, scattered fibroglandular densities, or heterogeneous or extreme density) and age (65-74 vs ≥75 years) was calculated using weighted means. Cox proportional hazards models were fit to estimate the association of breast density with invasive breast cancer risk. The likelihood ratio test was used to test the interaction between BMI and breast density. A total of 221 714 screening mammograms from 193 787 women were included in the study; a total of 38% of the study population was aged 75 years or older. Of the mammograms, most were from women aged 65 to 74 years (64.6%) and non-Hispanic White individuals (81.4%). The 5-year cumulative incidence of invasive breast cancer increased in association with increasing breast density among women aged 65 to 74 years (almost entirely fatty breasts: 11.3 per 1000 women [95% CI, 10.4-12.5 per 1000 women]; scattered fibroglandular densities: 17.2 per 1000 women [95% CI, 16.1-17.9 per 1000 women]; extremely or heterogeneously dense breasts: 23.7 per 1000 women [95% CI, 22.4-25.3 per 1000 women]) and among those aged 75 years or older (fatty breasts: 13.5 per 1000 women [95% CI, 11.6-15.5]; scattered fibroglandular densities: 18.4 per 1000 women [95% CI, 17.0-19.5 per 1000 women]; extremely or heterogeneously dense breasts: 22.5 per 1000 women [95% CI, 20.2-24.2 per 1000 women]). Extreme or heterogeneous breast density was associated with increased risk of breast cancer compared with scattered fibroglandular breast density in both age categories (65-74 years: hazard ratio [HR], 1.39 [95% CI, 1.28-1.50]; ≥75 years: HR, 1.23 [95% CI, 1.10-1.37]). Women with almost entirely fatty breasts had a decrease of approximately 30% (range, 27%-34%) in the risk of invasive breast cancer compared with women with scattered fibroglandular breast density (65-74 years: HR, 0.66 [95% CI, 0.58-0.75]; ≥75 years: HR, 0.73; 95% CI, 0.62-0.86). Associations between breast density and breast cancer risk were not significantly modified by BMI (for age 65-74 years: likelihood ratio test, 2.67; df, 2; P = .26; for age ≥75 years, 2.06; df, 2; P = .36). The findings suggest that breast density is associated with increased risk of invasive breast cancer among women aged 65 years or older. Breast density and life expectancy should be considered together when discussing the potential benefits vs harms of continued screening mammography in this population.

Abstract 2531: Function-related indicator and outcomes of screening mammography in older women from the BCSC-Medicare Cohort

Abstract Background: Although there is evidence pointing to the role of comorbidity and age in screening mammography outcomes among older women, the impact of functional decline on mortality in this population is unknown. Methods: We used data from 238,849 women in the Breast Cancer Surveillance Consortium-Medicare (BCSC) linked database from 1999-2015 who had at least one screening mammogram at ages 66-94 years. We estimated the 10-year cumulative incidence of breast cancer, breast cancer death, and non-breast cancer death by function-related indicator (FRI) which incorporated 16 claims-based items reflecting functional or health status in older people. In the analysis, FRI score was categorized as an ordinal variable (0, 1, and 2+) and a higher score indicated a higher burden of functional limitations. Fine and Gray proportional sub-distribution hazards models were applied with incident breast cancer and death treated as competing events. Risk estimates by FRI scores (0, 1, and 2+) were adjusted by age and NCI comorbidity index separately and stratified by these factors. Results: During a median follow-up of 101 months, 9,252 women were diagnosed with breast cancer. During follow-up, 406 women died of breast cancer and 41,640 died from non-breast cancer causes. The 10-year age-adjusted cumulative incidence of invasive breast cancer slightly decreased with increasing FRI score (FRI=0: 4.0%, 95% CI=3.8%-4.1%; FRI=1: 3.9%, 95% CI=3.7%-4.2%; FRI=2+: 3.5%, 95% CI=3.1%-3.9%). Risk of death from non-breast cancer causes increased with FRI score (FRI=0: 18.8%, 95% CI=18.5%-19.1%; FRI=1: 24.4%, 95% CI=23.9%-25.0%; FRI=2+: 39.8%, 95% CI=38.8%-40.9%). Risk of breast cancer death was low with minimal risk differences across FRI scores (FRI=0: 0.24%, 95%CI=0.20%-0.28%; FRI=1: 0.20%, 95%CI=0.14%-0.26%; FRI=2+: 0.30%, 95% CI=0.18%-0.42%). Risk estimates in NCI comorbidity index-adjusted models were largely similar to outcomes in age-adjusted models. Stratified analyses suggested similar patterns of risk estimates by FRI. Conclusion: Cumulative risk of death from non-breast cancer causes substantially increases with FRI score, suggesting that the potential of screening mammography to benefit older women is low among those with a high burden of functional limitation. Citation Format: Dongyu Zhang, Linn Abraham, Joshua Demb, Diana L. Miglioretti, Shailesh Advani, Brian L. Sprague, Louise M. Henderson, Tracy Onega, Karen Wernli, Louise C. Walter, Karla Kerlikowske, John T. Schousboe, Ellen S. O'Meara, Dejana Braithwaite. Function-related indicator and outcomes of screening mammography in older women from the BCSC-Medicare Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2531.

Breast cancer risk after age 60 amongBRCA1 andBRCA2 mutation carriers.

It is not known whether the risk of breast cancer among BRCA1 and BRCA2 mutation carriers after age 60 is high enough to justify intensive screening or prophylactic surgery. Thus, we conducted a prospective analysis of breast cancer risk in BRCA1 and BRCA2 mutation carriers from age 60 until age 80. Subjects had no history of cancer and both breasts intact at age 60 (n = 699). Women were followed until a breast cancer diagnosis, prophylactic bilateral mastectomy or death. We calculated the annual cancer rate and cumulative incidence of breast cancer (invasive and in situ) from age 60 to age 80. We assessed the associations between hormone replacement therapy, family history of breast cancer and bilateral oophorectomy and breast cancer risk. Over a mean follow-up of 7.9years, 61 invasive and 20 in situ breast cancers were diagnosed in the cohort. The mean annual rate of invasive breast cancer was 1.8% for BRCA1 mutation carriers and 1.7% for BRCA2 mutation carriers. The cumulative risk of invasive breast cancer from age 60 to 80 was 20.1% for women with a BRCA1 mutation and was 17.3% for women with a BRCA2 mutation. Hormone replacement therapy, family history and oophorectomy were not associated with breast cancer risk. Findings from this large prospective study indicate that the risk of developing breast cancer remains high after age 60 in both BRCA1 and BRCA2 mutation carriers. These findings warrant further evaluation of the role of breast cancer screening in older mutation carriers.