Search

Background: Breast cancer has been associated with monogenic, polygenic, and epidemiologic (clinical, reproductive and lifestyle) risk factors, but studies evaluating the combined effects of these factors have been limited., Methods: We extended previous work in breast cancer risk modeling, incorporating pathogenic variants (PV) in six breast cancer predisposition genes and a 105-SNP polygenic risk score (PRS), to include an epidemiologic risk score (ERS) in a sample of non-Hispanic White women drawn from prospective cohorts and population-based case-control studies, with 23,518 cases and 22,832 controls, from the Cancer Risk Estimates Related to Susceptibility (CARRIERS) Consortium., Results: The model predicts 4.4-fold higher risk of breast cancer for postmenopausal women with no predisposition PV and median PRS, but with the highest versus lowest ERS. Overall, women with CHEK2 PVs had >20% lifetime risk of breast cancer. However, 15.6% of women with CHEK2 PVs and a family history of breast cancer, and 45.1% of women with CHEK2 PVs but without a family history of breast cancer, had low (<20%) predicted lifetime risk and thus were below the threshold for MRI screening. CHEK2 PV carriers at the 10th percentile of the joint distribution of ERS and PRS, without a family history of breast cancer, had a predicted lifetime risk similar to the general population., Conclusions: These results illustrate that an ERS, alone and combined with the PRS, can contribute to clinically relevant risk stratification., Impact: Integrating monogenic, polygenic, and epidemiologic risk factors in breast cancer risk prediction models may inform personalized screening and prevention efforts.

Background: Breast cancer incidence rates in women of Asian descent have been increasing in the United States and Asia., Methods: In a case-control study of Asian American women from the San Francisco Bay Area, we assessed associations with birthplace and migration-related characteristics and compared risk factors between Asian American and non-Hispanic White women by birthplace and birth cohort., Results: Birthplace and migration-related characteristics were associated with breast cancer risk only among women in the younger birth cohort (1951-1984) that comprised 355 cases diagnosed at age ≤55 years and 276 sister and population controls. Breast cancer risk was marginally increased among foreign-born women [OR = 1.40; 95% confidence interval (CI), 0.97-2.03] and two-fold among foreign-born Chinese women (OR = 2.16; 95% CI, 1.21-3.88). Two-fold increased risks were associated with migration at age ≥40 years and longer U.S. residence (≥30 years or ≥75% of life). The education level was high among both cases and controls. Differences in the prevalence of risk factors by birthplace and birth cohort suggest temporal changes in reproductive and lifestyle-related factors. The prevalence in risk factors was similar between foreign-born and U.S.-born women in the younger birth cohort, and did not fully explain the observed associations with birthplace and other migration characteristics., Conclusions: In contrast to studies from earlier decades, younger foreign-born Asian American women had a higher risk of breast cancer than U.S.-born Asian American women., Impact: It is important and urgent to understand what factors drive the increasing burden of breast cancer in women of Asian descent and implement effective prevention programs., (©2023 American Association for Cancer Research.)

Background: Racial/ethnic disparities in cancer mortality are well described and are partly attributable to later stage of diagnosis. It is unclear to what extent reductions in the incidence of late-stage cancer could narrow these relative and absolute disparities., Methods: We obtained stage- and cancer-specific incidence and survival data from the Surveillance, Epidemiology, and End Results Program for persons ages 50 to 79 years between 2006 and 2015. For eight hypothetical cohorts of 100,000 persons defined by race/ethnicity and sex, we estimated cancer-related deaths if cancers diagnosed at stage IV were detected earlier, by assigning them outcomes of earlier stages., Results: We observed a 3-fold difference in the absolute burden of stage IV cancer between the group with the highest rate (non-Hispanic Black males, 337 per 100,000) and the lowest rate (non-Hispanic Asian/Pacific Islander females, 117 per 100,000). Assuming all stage IV cancers were diagnosed at stage III, 32-80 fewer cancer-related deaths would be expected across subgroups, a relative reduction of 13%-14%. Assuming one third of metastatic cancers were diagnosed at each earlier stage (I, II, and III), 52-126 fewer cancer-related deaths would be expected across subgroups, a relative reduction of 21%-23%., Conclusions: Across population subgroups, non-Hispanic Black males have the highest burden of stage IV cancer and would have the most deaths averted from improved detection of cancer before metastasis., Impact: Detecting cancer before metastasis could meaningfully reduce deaths in all populations, but especially in non-Hispanic Black populations. See related commentary by Loomans-Kropp et al., p. 512., (©2021 The Authors; Published by the American Association for Cancer Research.)

Background: Limited studies have investigated racial/ethnic survival disparities for breast cancer defined by estrogen receptor (ER) and progesterone receptor (PR) status in a multiethnic population., Methods: Using multivariable Cox proportional hazards models, we assessed associations of race/ethnicity with ER/PR-specific breast cancer mortality in 10,366 California women diagnosed with breast cancer from 1993 to 2009. We evaluated joint associations of race/ethnicity, health care, sociodemographic, and lifestyle factors with mortality., Results: Among women with ER/PR + breast cancer, breast cancer-specific mortality was similar among Hispanic and Asian American women, but higher among African American women [HR, 1.31; 95% confidence interval (CI), 1.05-1.63] compared with non-Hispanic White (NHW) women. Breast cancer-specific mortality was modified by surgery type, hospital type, education, neighborhood socioeconomic status (SES), smoking history, and alcohol consumption. Among African American women, breast cancer-specific mortality was higher among those treated at nonaccredited hospitals (HR, 1.57; 95% CI, 1.21-2.04) and those from lower SES neighborhoods (HR, 1.48; 95% CI, 1.16-1.88) compared with NHW women without these characteristics. Breast cancer-specific mortality was higher among African American women with at least some college education (HR, 1.42; 95% CI, 1.11-1.82) compared with NHW women with similar education. For ER - /PR - disease, breast cancer-specific mortality did not differ by race/ethnicity and associations of race/ethnicity with breast cancer-specific mortality varied only by neighborhood SES among African American women., Conclusions: Racial/ethnic survival disparities are more striking for ER/PR + than ER - /PR - breast cancer. Social determinants and lifestyle factors may explain some of the survival disparities for ER/PR + breast cancer., Impact: Addressing these factors may help reduce the higher mortality of African American women with ER/PR + breast cancer., (©2020 American Association for Cancer Research.)

Background: New technologies are being developed for early detection of multiple types of cancer simultaneously. To quantify the potential benefit, we estimated reductions in absolute cancer-related deaths that could occur if cancers diagnosed after metastasis (stage IV) were instead diagnosed at earlier stages., Methods: We obtained stage-specific incidence and survival data from the Surveillance, Epidemiology, and End Results Program for 17 cancer types for all persons diagnosed ages 50 to 79 years in 18 geographic regions between 2006 and 2015. For a hypothetical cohort of 100,000 persons, we estimated cancer-related deaths under assumptions that cancers diagnosed at stage IV were diagnosed at earlier stages., Results: Stage IV cancers represented 18% of all estimated diagnoses but 48% of all estimated cancer-related deaths within 5 years. Assuming all stage IV cancers were diagnosed at stage III, 51 fewer cancer-related deaths would be expected per 100,000, a reduction of 15% of all cancer-related deaths. Assuming one third of metastatic cancers were diagnosed at stage III, one third diagnosed at stage II, and one third diagnosed at stage I, 81 fewer cancer-related deaths would be expected per 100,000, a reduction of 24% of all cancer-related deaths, corresponding to a reduction in all-cause mortality comparable in magnitude to eliminating deaths due to cerebrovascular disease., Conclusions: Detection of multiple cancer types earlier than stage IV could reduce at least 15% of cancer-related deaths within 5 years, affecting not only cancer-specific but all-cause mortality., Impact: Detecting cancer before stage IV, including modest shifts to stage III, could offer substantial population benefit., (©2020 American Association for Cancer Research.)

Background: Population-representative risks of metastatic recurrence are not generally available because cancer registries do not collect data on recurrence. This article presents a novel method that estimates the risk of recurrence using cancer registry disease-specific survival. Methods: The method is based on an illness-death process coupled with a mixture cure model for net cancer survival. The risk of recurrence is inferred from the estimated survival among the noncured fraction and published data on survival after recurrence. We apply the method to disease-specific survival curves from female breast cancer cases without a prior cancer diagnosis and with complete stage and hormone receptor (HR) status in Surveillance, Epidemiology and End Results registries (1992-2013). Results: The risk of recurrence is higher for women diagnosed with breast cancer at older age, earlier period, more advanced stage, and HR-negative tumors. For women diagnosed at ages 60-74 in 2000-2013, the projected percent recurring within 5 years is 2.5%, 9.6%, and 34.5% for stages I, II, and III HR-positive, and 6.5%, 20.2%, and 48.5% for stages I, II, and III HR-negative tumors. Although HR-positive cases have lower risk of recurrence soon after diagnosis, their risk persists longer than for HR-negative cases. Results show a high degree of robustness to model assumptions. Conclusions: The results show that it is possible to extract information about the risk of recurrence using disease-specific survival, and the methods can in principle be extended to other cancer sites. Impact: This study provides the first population-based summaries of the risk of breast cancer recurrence in U.S. women. Cancer Epidemiol Biomarkers Prev; 27(11); 1332-41. ©2018 AACR., (©2018 American Association for Cancer Research.)

Background: Although incidence rates of breast cancer molecular subtypes are well documented, effects of molecular subtypes on breast cancer-specific survival using the largest population coverage to date are unknown in the U.S., Population: Methods: Using Surveillance, Epidemiology and End Results cancer registry data, we assessed survival after breast cancer diagnosis among women diagnosed during 2010 to 2013 and followed through December 31, 2014. Breast cancer molecular subtypes defined by joint hormone receptor [HR, estrogen receptor (ER) and/or progesterone receptor (PR)] and HER2 status were assessed. Multiple imputation was used to fill in missing receptor status. Four-year breast cancer-specific survival per molecular subtypes and clinical/demographic factors were calculated. A Cox proportional hazards model was used to evaluate survival while controlling for clinical and demographic factors. Results: The best survival pattern was observed among women with HR + /HER2 - subtype (survival rate of 92.5% at 4 years), followed by HR + /HER2 + (90.3%), HR - /HER2 + (82.7%), and finally worst survival for triple-negative subtype (77.0%). Notably, failing to impute cases with missing receptor status leads to overestimation of survival because those with missing receptor status tend to have worse prognostic features. Survival differed substantially by stage at diagnosis. Among de novo stage IV disease, women with HR + /HER2 + subtype experienced better survival than those with HR + /HER2 - subtype (45.5% vs. 35.9%), even after controlling for other factors. Conclusions: Divergence of survival curves in stage IV HR + /HER2 + versus HR + /HER2 - subtype is likely attributable to major advances in HER2-targeted treatment. Impact: Contrary to conventional thought, HR + /HER2 + subtype experienced better survival than HR + /HER2 - in advanced-stage disease. Cancer Epidemiol Biomarkers Prev; 27(6); 619-26. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Background: Racial/ethnic disparity in breast cancer-specific mortality in the United States is well documented. We examined whether accounting for racial/ethnic differences in the prevalence of clinical, patient, and lifestyle and contextual factors that are associated with breast cancer-specific mortality can explain this disparity., Methods: The California Breast Cancer Survivorship Consortium combined interview data from six California-based breast cancer studies with cancer registry data to create a large, racially diverse cohort of women with primary invasive breast cancer. We examined the contribution of variables in a previously reported Cox regression baseline model plus additional contextual, physical activity, body size, and comorbidity variables to the racial/ethnic disparity in breast cancer-specific mortality., Results: The cohort comprised 12,098 women. Fifty-four percent were non-Latina Whites, 17% African Americans, 17% Latinas, and 12% Asian Americans. In a model adjusting only for age and study, breast cancer-specific HRs relative to Whites were 1.69 (95% CI, 1.46-1.96), 1.00 (0.84-1.19), and 0.52 (0.33-0.85) for African Americans, Latinas, and Asian Americans, respectively. Adjusting for baseline-model variables decreased disparity primarily by reducing the HR for African Americans to 1.13 (0.96-1.33). The most influential variables were related to disease characteristics, neighborhood socioeconomic status, and smoking status at diagnosis. Other variables had negligible impact on disparity., Conclusions: Although contextual, physical activity, body size, and comorbidity variables may influence breast cancer-specific mortality, they do not explain racial/ethnic mortality disparity., Impact: Other factors besides those investigated here may explain the existing racial/ethnic disparity in mortality. Cancer Epidemiol Biomarkers Prev; 25(7); 1064-72. ©2016 AACR., (©2016 American Association for Cancer Research.)

Little is known about neighborhood attributes that may influence opportunities for healthy eating and physical activity in relation to breast cancer mortality. We used data from the California Breast Cancer Survivorship Consortium and the California Neighborhoods Data System (CNDS) to examine the neighborhood environment, body mass index, and mortality after breast cancer. We studied 8,995 African American, Asian American, Latina, and non-Latina white women with breast cancer. Residential addresses were linked to the CNDS to characterize neighborhoods. We used multinomial logistic regression to evaluate the associations between neighborhood factors and obesity and Cox proportional hazards regression to examine associations between neighborhood factors and mortality. For Latinas, obesity was associated with more neighborhood crowding [quartile 4 (Q4) vs. Q1: OR, 3.24; 95% confidence interval (CI), 1.50-7.00]; breast cancer-specific mortality was inversely associated with neighborhood businesses (Q4 vs. Q1: HR, 0.46; 95% CI, 0.25-0.85) and positively associated with multifamily housing (Q3 vs. Q1: HR, 1.98; 95% CI, 1.20-3.26). For non-Latina whites, lower neighborhood socioeconomic status (SES) was associated with obesity [quintile 1 (Q1) vs. Q5: OR, 2.52; 95% CI, 1.31-4.84], breast cancer-specific (Q1 vs. Q5: HR, 2.75; 95% CI, 1.47-5.12), and all-cause (Q1 vs. Q5: HR, 1.75; 95% CI, 1.17-2.62) mortality. For Asian Americans, no associations were seen. For African Americans, lower neighborhood SES was associated with lower mortality in a nonlinear fashion. Attributes of the neighborhood environment were associated with obesity and mortality following breast cancer diagnosis, but these associations differed across racial/ethnic groups., (©2015 American Association for Cancer Research.)

Background: Higher breast cancer mortality rates for African-American than non-Hispanic White women are well documented; however, it remains uncertain if this disparity occurs in disease subgroups defined by tumor molecular markers and stage at diagnosis. We examined racial differences in outcome according to subtype and stage in a diverse, population-based series of 103,498 patients., Methods: We obtained data for all invasive breast cancers diagnosed between January 1, 2005, and December 31, 2012, and followed through December 31, 2012, among 93,760 non-Hispanic White and 9,738 African-American women in California. Molecular subtypes were categorized according to tumor expression of hormone receptor (HR, based on estrogen and progesterone receptors) and human epidermal growth factor receptor 2 (HER2). Cox proportional hazards models were used to calculate relative hazard (RH) and 95% confidence intervals (CI) for breast cancer-specific mortality., Results: After adjustment for patient, tumor, and treatment characteristics, outcomes were comparable by race for stage I or IV cancer regardless of subtype, and HR(+)/HER2(+) or HR(-)/HER2(+) cancer regardless of stage. We found substantially higher hazards of breast cancer death among African-American women with stage II/III HR(+)/HER2(-) (RH, 1.31; 95% CI, 1.03-1.65; and RH, 1.39; 95% CI, 1.10-1.75, respectively) and stage III triple-negative cancers relative to Whites., Conclusions: There are substantial racial/ethnic disparities among patients with stages II/III HR(+)/HER2(-) and stage III triple-negative breast cancers but not for other subtype and stage., Impact: These data provide insights to assess barriers to targeted treatment (e.g., trastuzumab or endocrine therapy) of particular subtypes of breast cancer among African-American patients., (©2015 American Association for Cancer Research.)

Background: The role of comorbidities in survival of patients with breast cancer has not been well studied, particularly in non-white populations., Methods: We investigated the association of specific comorbidities with mortality in a multiethnic cohort of 8,952 breast cancer cases within the California Breast Cancer Survivorship Consortium (CBCSC), which pooled questionnaire and cancer registry data from five California-based studies. In total, 2,187 deaths (1,122 from breast cancer) were observed through December 31, 2010. Using multivariable Cox proportional hazards regression, we estimated HRs and 95% confidence intervals (CI) for overall and breast cancer-specific mortality associated with previous cancer, diabetes, high blood pressure (HBP), and myocardial infarction., Results: Risk of breast cancer-specific mortality increased among breast cancer cases with a history of diabetes (HR, 1.48; 95% CI, 1.18-1.87) or myocardial infarction (HR, 1.94; 95% CI, 1.27-2.97). Risk patterns were similar across race/ethnicity (non-Latina white, Latina, African American, and Asian American), body size, menopausal status, and stage at diagnosis. In subgroup analyses, risk of breast cancer-specific mortality was significantly elevated among cases with diabetes who received neither radiotherapy nor chemotherapy (HR, 2.11; 95% CI, 1.32-3.36); no increased risk was observed among those who received both treatments (HR, 1.13; 95% CI, 0.70-1.84; P(interaction) = 0.03). A similar pattern was found for myocardial infarction by radiotherapy and chemotherapy (P(interaction) = 0.09)., Conclusion: These results may inform future treatment guidelines for patients with breast cancer with a history of diabetes or myocardial infarction., Impact: Given the growing number of breast cancer survivors worldwide, we need to better understand how comorbidities may adversely affect treatment decisions and ultimately outcome., (©2014 American Association for Cancer Research.)

Background: Women with inherited mutations in the BRCA1 or BRCA2 (BRCA1/2) genes are recommended to undergo a number of intensive cancer risk-reducing strategies, including prophylactic mastectomy, prophylactic oophorectomy, and screening. We estimate the impact of different risk-reducing options at various ages on life expectancy., Methods: We apply our previously developed Monte Carlo simulation model of screening and prophylactic surgery in BRCA1/2 mutation carriers. Here, we present the mathematical formulation to compute age-specific breast cancer incidence in the absence of prophylactic oophorectomy, which is an input to the simulation model, and provide sensitivity analysis on related model parameters., Results: The greatest gains in life expectancy result from conducting prophylactic mastectomy and prophylactic oophorectomy immediately after BRCA1/2 mutation testing; these gains vary with age at testing, from 6.8 to 10.3 years for BRCA1 and 3.4 to 4.4 years for BRCA2 mutation carriers. Life expectancy gains from delaying prophylactic surgery by 5 to 10 years range from 1 to 9.9 years for BRCA1 and 0.5 to 4.2 years for BRCA2 mutation carriers. Adding annual breast screening provides gains of 2.0 to 9.9 years for BRCA1 and 1.5 to 4.3 years for BRCA2. Results were most sensitive to variations in our assumptions about the magnitude and duration of breast cancer risk reduction due to prophylactic oophorectomy., Conclusions: Life expectancy gains depend on the type of BRCA mutation and age at interventions. Sensitivity analysis identifies the degree of breast cancer risk reduction due to prophylactic oophorectomy as a key determinant of life expectancy gain., Impact: Further study of the impact of prophylactic oophorectomy on breast cancer risk in BRCA1/2 mutation carriers is warranted., (©2012 AACR)

Background: Clinical guidelines recommend breast-conserving surgery (BCS) with radiation as a viable alternative to mastectomy for treatment of early-stage breast cancer. Yet, Asian Americans are more likely than other groups to have mastectomy or omit radiation after BCS., Methods: We applied polytomous logistic regression and recursive partitioning to analyze factors associated with mastectomy, or BCS without radiation, among 20,987 California Asian Americans diagnosed with stage 0 to II breast cancer from 1990 to 2007., Results: The percentage receiving mastectomy ranged from 40% among U.S.-born Chinese to 58% among foreign-born Vietnamese. Factors associated with mastectomy included tumor characteristics such as larger tumor size, patient characteristics such as older age and foreign birthplace among some Asian Americans ethnicities, and additional factors including hospital [smaller hospital size, not National Cancer Institute cancer center, low socioeconomic status (SES) patient composition, and high hospital Asian Americans patient composition] and neighborhood characteristics (ethnic enclaves of low SES). These hospital and neighborhood characteristics were also associated with BCS without radiation. Through recursive partitioning, the highest mastectomy subgroups were defined by tumor characteristics such as size and anatomic location, in combination with diagnosis year and nativity., Conclusions: Tumor characteristics and, secondarily, patient, hospital, and neighborhood factors are predictors of mastectomy and omission of radiation following BCS among Asian Americans., Impact: By focusing on interactions among patient, hospital, and neighborhood factors in the differential receipt of breast cancer treatment, our study identifies subgroups of interest for further study and translation into public health and patient-focused initiatives to ensure that all women are fully informed about treatment options.

Purpose: Patients with early-onset breast and/or ovarian cancer frequently wish to know if they inherited a mutation in one of the cancer susceptibility genes, BRCA1 or BRCA2. Accurate carrier prediction models are needed to target costly testing. Two widely used models, BRCAPRO and BOADICEA, were developed using data from non-Hispanic Whites (NHW), but their accuracies have not been evaluated in other racial/ethnic populations., Methods: We evaluated the BRCAPRO and BOADICEA models in a population-based series of African American, Hispanic, and NHW breast cancer patients tested for BRCA1 and BRCA2 mutations. We assessed model calibration by evaluating observed versus predicted mutations and attribute diagrams, and model discrimination using areas under the receiver operating characteristic curves., Results: Both models were well-calibrated within each racial/ethnic group, with some exceptions. BOADICEA overpredicted mutations in African Americans and older NHWs, and BRCAPRO underpredicted in Hispanics. In all racial/ethnic groups, the models overpredicted in cases whose personal and family histories indicated >80% probability of carriage. The two models showed similar discrimination in each racial/ethnic group, discriminating least well in Hispanics. For example, BRCAPRO's areas under the receiver operating characteristic curves were 83% (95% confidence interval, 63-93%) for NHWs, compared with 74% (59-85%) for African Americans and 58% (45-70%) for Hispanics., Conclusions: The poor performance of the model for Hispanics may be due to model misspecification in this racial/ethnic group. However, it may also reflect racial/ethnic differences in the distributions of personal and family histories among breast cancer cases in the Northern California population.

Objective: Nipple fluid production and atypical breast duct cells in women at high risk of breast cancer have been associated with further increased risk. Most publications on ductal lavage for cell collection report cannulating fluid-yielding ducts only. We report lavage of fluid-yielding and non-fluid-yielding ducts in women at high inherited breast cancer risk., Methods: A pilot breast cancer screening study including ductal lavage was conducted in 75 women at high inherited risk, 56 (74.7%) of whom had BRCA1/2 mutations. Ductal lavage was attempted in any duct identifiable with a catheter., Results: Ducts were successfully catheterized in 60 of 75 patients (80%). Successfully catheterized patients were younger (median age 41 versus 53 years, P = 0.0003) and more often premenopausal (51.7% versus 20%, P = 0.041). Thirty-one successfully catheterized patients [51.6%, 95% confidence interval (39.4-63.9%)] had non-fluid-yielding ducts only. Seventeen patients [28.3% (18.5-40.9%)] had atypical cells. Twelve of seventeen [70.6% (46.8-87.2%)] samples with atypia were from non-fluid-yielding ducts. Patients with non-fluid-yielding ducts (versus fluid-yielding ducts) were more likely to have had prior cancer (48.4% versus 17.2%, P = 0.014) or chemotherapy (45.2% versus 17.2%, P = 0.027); this was also true in patients with atypia from non-fluid-yielding ducts., Conclusion: Successfully lavaged women were younger and more often premenopausal. Atypical cells can be found in non-fluid-yielding ducts in patients at high inherited breast cancer risk. Non-fluid-yielding ducts, and atypia from non-fluid-yielding ducts, are more common in patients with prior cancer and chemotherapy. Larger studies are needed to identify risk factors and prognostic significance associated with atypia and non-fluid-yielding ducts in high-risk populations, and define their role as biomarkers.