Faculty Bibliography

Approximately 5%-10% of breast cancers are due to genetic predisposition caused by germline mutations; the most commonly tested genes are BRCA1 and BRCA2 mutations. Some mutations are unique to one family and others are recurrent; the spectrum of BRCA1/BRCA2 mutations varies depending on the geographical origins, populations or ethnic groups. In this review, we compiled data from 11 participating Asian countries (Bangladesh, Mainland China, Hong Kong SAR, Indonesia, Japan, Korea, Malaysia, Philippines, Singapore, Thailand and Vietnam), and from ethnic Asians residing in Canada and the USA. We have additionally conducted a literature review to include other Asian countries mainly in Central and Western Asia. We present the current pathogenic mutation spectrum of BRCA1/BRCA2 genes in patients with breast cancer in various Asian populations. Understanding BRCA1/BRCA2 mutations in Asians will help provide better risk assessment and clinical management of breast cancer.

The role of the lifetime number of ovulatory cycles has not been evaluated in the context of BRCA-associated ovarian cancer. Thus, we conducted a matched case-control study to evaluate the relationship between the cumulative number of ovulatory cycles (and contributing components) and risk of developing ovarian cancer in BRCA mutation carriers (1,329 cases and 5,267 controls). Information regarding reproductive and hormonal factors was collected from a routinely administered questionnaire. Conditional logistic regression was used to evaluate all associations. We observed a 45% reduction in the risk of developing ovarian cancer among women in the lowest vs. highest quartile of ovulatory cycles (OR = 0.55; 95% CI 0.41-0.75, p = 0.0001). Breastfeeding for more than 12 months was associated with a 38% (95% CI 0.48-0.79) and 50% (95% CI 0.29-0.84) reduction in risk among BRCA1 and BRCA2 mutation carriers, respectively. For oral contraceptive use, maximum benefit was seen with five or more years of use among BRCA1 mutation carriers (OR = 0.50; 95% CI 0.40-0.63) and three or more years for BRCA2 mutation carriers (OR = 0.42; 95% CI 0.22-0.83). Increasing parity was associated with a significant inverse trend among BRCA1 (OR = 0.87; 95% CI 0.79-0.96; p-trend = 0.005) but not BRCA2 mutation carriers (OR 0.98; 95% CI 0.81-1.19; p-trend = 0.85). A later age at menopause was associated with an increased risk in women with a BRCA1 mutation (OR trend = 1.18; 95% CI 1.03-1.35; p = 0.02). These findings support an important role of breastfeeding and oral contraceptive use for the primary prevention of ovarian cancer among women carrying BRCA mutations.

Background. The incidence of premenopausal breast cancer is rising throughout South Asia. Our objective was to determine the role of risk factors associated with Westernization for premenopausal breast cancer in Bangladesh. Methods. We conducted a matched case-control study between January 1, 2007, and December 31, 2010, at four hospitals in Bangladesh. Cases were premenopausal women diagnosed with invasive breast cancer. Controls were premenopausal women with no personal history of breast cancer. Logistic regression was used to calculate the odds ratios (OR) for breast cancer. Results. We identified 129 age-matched pairs. The mean age of breast cancer diagnosis was 37.5 years. Each year decrease in the age of menarche significantly increased the risk of breast cancer (OR = 1.67, 95% CI 1.09-2.56, P = 0.02). The risk was also increased with a current body mass index of >/=25 kg/m(2) (OR = 5.24, 95% CI 1.10-24.9, P = 0.04). Age at first childbirth, parity, and breastfeeding were not significantly associated with premenopausal breast cancer risk (P > 0.05). Conclusions. Age at menarche and adult weight gain were associated with premenopausal breast cancer risk. Other factors associated with Westernization may not be relevant to premenopausal breast cancer risk in Bangladesh.

Women with diabetes have higher breast cancer incidence and mortality. The purpose of this study was to examine the impact of diabetes on stage at breast cancer diagnosis, as a possible reason for their higher mortality. Using population-based health databases from Ontario, Canada, this retrospective cohort study examined stage at diagnosis (II, III, or IV vs I) among women aged 20-105 years who were newly diagnosed with invasive breast cancer between 2007 and 2012. We compared those with diabetes to those without diabetes. Diabetes was defined based on medical records using a validated algorithm. Among 38,407 women with breast cancer, 6115 (15.9 %) women had diabetes. Breast cancer patients with diabetes were significantly more likely to present with advanced-stage breast cancer than those without diabetes. After adjustment for mammograms and other covariates, diabetes was associated with a significantly increased risk of Stage II [adjusted odds ratio (aOR) 1.14, 95 % confidence interval (CI) 1.07, 1.22], Stage III (aOR 1.21, 95 % CI 1.11, 1.33), and Stage IV (aOR 1.16, 95 % CI 1.01, 1.33) versus Stage I breast cancer. Women with diabetes had a higher risk of lymph node metastases (aOR 1.16, 95 % CI 1.06, 1.27) and tumors with size over 2 cm (aOR 1.16, 95 % CI 1.06, 1.28). Diabetes was associated with more advanced-stage breast cancer, even after accounting for differences in screening mammogram use and other factors. Our findings suggest that diabetes may predispose to more aggressive breast cancer, which may be a contributor to their higher cancer mortality.

IMPORTANCE: Women with early-stage breast cancers are expected to have excellent survival rates. It is important to identify factors that predict diagnosis of early-stage breast cancers. OBJECTIVE: To determine the proportion of breast cancers that were identified at an early stage (stage I) in different racial/ethnic groups and whether ethnic differences may be better explained by early detection or by intrinsic biological differences in tumor aggressiveness. DESIGN, SETTING, AND PARTICIPANTS: Observational study of women diagnosed with invasive breast cancer from 2004 to 2011 who were identified in the Surveillance, Epidemiology, and End Results (SEER) 18 registries database (N = 452,215). For each of 8 racial/ethnic groups, biological aggressiveness (triple-negative cancers, lymph node metastases, and distant metastases) of small-sized tumors of 2.0 cm or less was estimated. The odds ratio (OR) for being diagnosed at stage I compared with a later stage and the hazard ratio (HR) for death from stage I breast cancer by racial/ethnic group were determined. The date of final follow-up was December 31, 2011. MAIN OUTCOMES AND MEASURES: Breast cancer stage at diagnosis and 7-year breast cancer-specific survival, adjusted for age at diagnosis, income, and estrogen receptor status. RESULTS: Of 373,563 women with invasive breast cancer, 268,675 (71.9%) were non-Hispanic white; 34,928 (9.4%), Hispanic white; 38,751 (10.4%), black; 25,211 (6.7%), Asian; and 5998 (1.6%), other ethnicities. Mean follow-up time was 40.6 months (median, 38 months). Compared with non-Hispanic white women diagnosed with stage I breast cancer (50.8%), Japanese women (56.1%) were more likely to be diagnosed (OR, 1.23 [95% CI, 1.15-1.31], P < .001) and black women (37.0%) were less likely to be diagnosed (OR, 0.65 [95% CI, 0.64-0.67], P < .001). Actuarial risk of death from stage I breast cancer at 7 years was higher among black women (6.2%) than non-Hispanic white women (3.0%) (HR, 1.57 [95% CI, 1.40-1.75]; P < .001), and lower among South Asian women (1.7%) (HR, 0.48 [95% CI, 0.20-1.15]; P = .10). Black women were more likely to die of breast cancer with small-sized tumors (9.0%) than non-Hispanic white women (4.6%) (HR, 1.96 [95% CI, 1.82-2.12]; P < .001); the difference remained after adjustment for income and estrogen receptor status (HR, 1.56 [95% CI, 1.45-1.69]; P < .001). CONCLUSIONS AND RELEVANCE: Among US women diagnosed with invasive breast cancer, the likelihood of diagnosis at an early stage, and survival after stage I diagnosis, varied by race and ethnicity. Much of the difference could be statistically accounted for by intrinsic biological differences such as lymph node metastasis, distant metastasis, and triple-negative behavior of tumors.

BACKGROUND: Breast cancer stage at diagnosis is an important predictor of survival. Our goal was to compare breast cancer stage at diagnosis (by American Joint Committee on Cancer criteria) in Chinese and South Asian women with stage at diagnosis in the remaining general population in Ontario. METHODS: We used the Ontario population-based cancer registry to identify all women diagnosed with breast cancer during 2005-2010, and we applied a validated surname algorithm to identify South Asian and Chinese women. We used logistic regression to compare, for Chinese or South Asian women and for the remaining general population, the frequency of diagnoses at stage ii compared with stage i and stages ii-iv compared with stage i. RESULTS: The registry search identified 1304 Chinese women, 705 South Asian women, and 39,287 women in the remaining general population. The Chinese and South Asian populations were younger than the remaining population (mean: 54, 57, and 61 years respectively). Adjusted for age, South Asian women were more often diagnosed with breast cancer at stage ii than at stage i [odds ratio (or): 1.28; 95% confidence interval (ci): 1.08 to 1.51] or at stages ii-iv than at stage i (or: 1.27; 95% ci: 1.08 to 1.48); Chinese women were less likely to be diagnosed at stage ii than at stage i (or: 0.82; 95% ci: 0.72 to 0.92) or at stages ii-iv than at stage i (or: 0.73; 95% ci: 0.65 to 0.82). CONCLUSIONS: Breast cancers were diagnosed at a later stage in South Asian women and at an earlier stage in Chinese women than in the remaining population. A more detailed analysis of ethnocultural factors influencing breast screening uptake, retention, and care-seeking behavior might be needed to help inform and evaluate tailored health promotion activities.