Breast Cancer Family History and Contralateral Breast Cancer Risk in Young Women: An Update From the Women’s Environmental Cancer and Radiation Epidemiology Study

Abstract

Purpose The Women's Environmental Cancer and Radiation Epidemiology (WECARE) study demonstrated the importance of breast cancer family history on contralateral breast cancer (CBC) risk, even for noncarriers of deleterious BRCA1/2 mutations. With the completion of WECARE II, updated risk estimates are reported. Additional analyses that exclude women negative for deleterious mutations in ATM, CHEK2*1100delC, and PALB2 were performed. Patients and Methods The WECARE Study is a population-based case-control study that compared 1,521 CBC cases with 2,212 individually matched unilateral breast cancer (UBC) controls. Participants were younger than age 55 years when diagnosed with a first invasive breast cancer between 1985 and 2008. Women were interviewed about breast cancer risk factors, including family history. A subset of women was screened for deleterious mutations in BRCA1/2, ATM, CHEK2*1100delC, and PALB2. Rate ratios (RRs) were estimated using multivariable conditional logistic regression. Cumulative absolute risks (ARs) were estimated by combining RRs from the WECARE Study and population-based SEER*Stat cancer incidence data. Results Women with any first-degree relative with breast cancer had a 10-year AR of 8.1% for CBC (95% CI, 6.7% to 9.8%). Risks also were increased if the relative was diagnosed at an age younger than 40 years (10-year AR, 13.5%; 95% CI, 8.8% to 20.8%) or with CBC (10-year AR, 14.1%; 95% CI, 9.5% to 20.7%). These risks are comparable with those seen in BRCA1/2 deleterious mutation carriers (10-year AR, 18.4%; 95% CI, 16.0% to 21.3%). In the subset of women who tested negative for deleterious mutations in BRCA1/2, ATM, CHEK2*1100delC, and PALB2, estimates were unchanged. Adjustment for known breast cancer single-nucleotide polymorphisms did not affect estimates. Conclusion Breast cancer family history confers a high CBC risk, even after excluding women with deleterious mutations. Clinicians are urged to use detailed family histories to guide treatment and future screening decisions for young women with breast cancer.

Magnitude of reduction in risk of second contralateral breast cancer with bilateral mastectomy in patients with breast cancer: Data from California, 1998 through 2015

“…Previous studies have shown that the incidence of second contralateral breast cancer varies according to patient characteristics, with greater risk reported among younger women with ER/PR‐negative tumors . This likely reflects the higher prevalence of hereditary pathogenic variants in BRCA1 /2 and other DNA repair genes within this patient subpopulation; however, a recent study also reported a high risk of second contralateral breast cancers among women with a family history of breast cancer, even when genetic testing was negative . Unlike survivors of ER/PR‐positive cancers, survivors of ER/PR‐negative tumors do not undergo adjuvant endocrine therapy, which has the beneficial side effect of reducing their risk of a second breast cancer .…”

“…[31][32][33][34] This likely reflects the higher prevalence of hereditary pathogenic variants in BRCA1/2 and other DNA repair genes within this patient subpopulation [33][34][35][36] ; however, a recent study also reported a high risk of second contralateral breast cancers among women with a family history of breast cancer, even when genetic testing was negative. 37 Unlike survivors of ER/PR-positive cancers, survivors of ER/PR-negative tumors do not undergo adjuvant endocrine therapy, which has the beneficial side effect of reducing their risk of a second breast cancer. 38 As in prior studies, 30,[32][33][34]37 we found a significant increase in the risk of second breast cancer among women aged <50 years at the time of initial diagnosis and/or with ER/PR-negative disease.…”

“…37 Unlike survivors of ER/PR-positive cancers, survivors of ER/PR-negative tumors do not undergo adjuvant endocrine therapy, which has the beneficial side effect of reducing their risk of a second breast cancer. 38 As in prior studies, 30,[32][33][34]37 we found a significant increase in the risk of second breast cancer among women aged <50 years at the time of initial diagnosis and/or with ER/PR-negative disease. These findings are consistent with clinical practice guidelines that advise genetic counseling and testing among women diagnosed at age <50 years or with triple-negative breast cancer.…”

A Deep Learning Mammography-based Model for Improved Breast Cancer Risk Prediction

“…S ince the creation of the Gail model in 1989 (1), risk models have supported risk-adjusted screening and prevention and their continued evolution has been a central pillar of breast cancer research (1)(2)(3)(4)(5)(6)(7)(8). Previous research (2,3) explored multiple risk factors related to hormonal and genetic information.…”

Machine Learning Methods to Identify Genetic Correlates of Radiation-Associated Contralateral Breast Cancer in the WECARE Study

“…Radiation-associated contralateral breast cancer (RCBC) is a rare adverse health outcome following radiation therapy for primary breast cancer; young women at the time of exposure are at greater risk than older women [1][2][3][4] . A number of risk or modifying factors have been found to be associated with developing contralateral breast cancer (CBC) such as the number of full-term pregnancies 5 , age at menarche [6][7][8] , treatment with chemotherapy or duration of tamoxifen therapy for first breast cancer [9][10][11] , family history of breast cancer [12][13][14] , and radiotherapy dose 3,15 . Genetic factors also have been identified [16][17][18][19][20] suggesting that certain rare genetic variations in deoxyribonucleic acid (DNA) damage response genes such as ATM might make it difficult to repair the damage induced by radiation and eventually may lead to CBC.…”