Faculty Bibliography

BACKGROUND: Breast reconstruction is an option for women with BRCA1 or BRCA2 mutations who elect to undergo prophylactic mastectomy to prevent breast cancer. We report on the uptake of breast reconstruction after prophylactic mastectomy in women with BRCA mutations from eight countries. METHODS: Women with a BRCA1 or BRCA2 mutation were questioned regarding their cancer preventive practices. Information was recorded on prophylactic mastectomy and breast reconstruction. RESULTS: A total of 1,635 women with a BRCA1 or BRCA2 mutation who elected to undergo prophylactic mastectomy from eight countries were included. A total of 1,137 women (69.5%) had breast reconstruction after prophylactic mastectomy. A total of 58.7% of women over the age of 45 years at the time of prophylactic mastectomy had breast reconstruction compared to 77.6% of women 35 years of age or younger [odds ratio (OR) 0.36, 95% confidence interval (CI) 0.26-0.50, p < 0.001]. In addition, 62.9% of women with a breast cancer diagnosis (contralateral prophylactic mastectomy) had breast reconstruction after prophylactic mastectomy compared to 79.7% of women without a previous breast cancer diagnosis (OR 0.48, 95% CI 0.38-0.61, p < 0.001). A total of 66.9% of women from Canada had breast reconstruction after mastectomy compared to 71.9% of American women (OR 0.75, 95% CI 0.59-0.96, p = 0.02). CONCLUSIONS: The majority of women elect for breast reconstruction after prophylactic mastectomy. However, younger women and those without a previous diagnosis of breast cancer are more likely to have breast reconstruction than older women or those with a previous diagnosis of cancer.

Breast cancer patients may have unmet supportive care needs during treatment, including symptom management of treatment-related toxicities, and educational, psychosocial, and spiritual needs. Delivery of supportive care is often a low priority in low- and middle-income settings, and is also dependent on resources available. This consensus statement describes twelve key recommendations for supportive care during treatment in low- and middle-income countries, identified by an expert international panel as part of the 5th Breast Health Global Initiative (BHGI) Global Summit for Supportive Care, which was held in October 2012, in Vienna, Austria. Panel recommendations are presented in a 4-tier resource-stratified table to illustrate how health systems can provide supportive care services during treatment to breast cancer patients, starting at a basic level of resource allocation and incrementally adding program resources as they become available. These recommendations include: health professional and patient and family education; management of treatment related toxicities, management of treatment-related symptoms of fatigue, insomnia and non-specific pain, and management of psychosocial and spiritual issues related to breast cancer treatment. Establishing supportive care during breast cancer treatment will help ensure that breast cancer patients receive comprehensive care that can help 1) improve adherence to treatment recommendations, 2) manage treatment-related toxicities and other treatment related symptoms, and 3) address the psychosocial and spiritual aspects of breast cancer and breast cancer treatments.

The objective is to estimate the risk of breast cancer in women who carry a deleterious BRCA1 or BRCA2 mutation, according to parental origin of mutation. We conducted a cohort study of women with a BRCA1 mutation (n = 1523) or BRCA2 mutation (n = 369) who had not been diagnosed with breast or ovarian cancer. For each woman, the pedigree was reviewed and the origin of the mutation was assigned as probable paternal or maternal. The hazard ratio (HR) for developing breast cancer in the follow-up period was estimated for women with a paternal mutation compared to a maternal mutation. The risk of breast cancer was modestly higher in women with a paternal BRCA1 mutation compared to women with a maternal BRCA1 mutation (HR = 1.46; 95% CI = 0.99-2.16) but the difference was not significant (p = 0.06). The parental mutation origin did not affect the risk in women with a BRCA2 mutation. Our results are consistent with the hypothesis that there is an increased risk of breast cancer among women with a paternally inherited BRCA1 mutation compared to a maternally inherited mutation. However, the data are not sufficiently compelling to justify different screening recommendations for the two subgroups.

OBJECTIVE: To evaluate the risk of endometrial cancer in women who carry a mutation in the BRCA1 or the BRCA2 gene. METHODS: We followed 4456 women with a BRCA1 or a BRCA2 mutation for incident cases of endometrial cancer. The incidence of endometrial cancer was estimated per 100,000 women per year. The hazard ratios for endometrial cancer were estimated by calculating standardized incidence ratios (SIRs) according to age group and country of residence. We estimated the impact of tamoxifen and hormone replacement therapy on the incidence of endometrial cancer in BRCA1 and BRCA2 carriers. RESULTS: After a mean follow-up of 5.7 years, we identified 17 endometrial cancers (13 cases in BRCA1 and 4 cases in BRCA2). The SIR for BRCA1 carriers was 1.91 (95% CI: 1.06-3.19, p=0.03) and for BRCA2 carriers was 1.75 (95% CI: 0.55-4.23, p=0.2). The SIR was 4.14 (95% CI: 1.92 to 7.87) for women who received tamoxifen and was 1.67 (95% CI: 0.81 to 3.07) for women who did not receive tamoxifen. The ten-year cumulative risk of endometrial cancer in women who were treated with tamoxifen was 2.0%. CONCLUSIONS: The risk of endometrial cancer is higher in BRCA1 mutation carriers than in the general population. The excessive risk is largely attributable to a history of tamoxifen use, but the actual risk of endometrial cancer associated with tamoxifen is small. It is important to discuss hysterectomy at the time of prophylactic bilateral salpingo-oophorectomy if tamoxifen is to be considered.

OBJECTIVE: To evaluate the impact of carrying a BRCA1 or BRCA2 mutation on the probability of experiencing premature natural menopause. DESIGN: Observational study. SETTING: Patients in an academic research environment. PATIENT(S): Women who carry a BRCA1 or BRCA2 mutation (case subjects) and women who do not carry a mutation (control subjects). INTERVENTION(S): Survey about reproductive history administered on study entry and every 2 years thereafter. MAIN OUTCOME MEASURE(S): The impact of carrying a BRCA mutation on age at menopause and other factors, including parity, age at first birth, age at last birth, and self-reported fertility. RESULT(S): A total of 908 matched pairs were identified. The mean age at natural menopause was 48.8 years for BRCA1 carriers, 49.2 years for BRCA2 carriers, and 50.3 years for control subjects. Women who carried a BRCA mutation had parity similar to noncarriers and were as likely as noncarriers to have a child after age 35 years. Similar proportions reported a history of fertility problems (12.5% vs. 13.7%) and use of fertility medication (6.0% vs. 7.0%). CONCLUSION(S): Women who carry a BRCA mutation experience menopause earlier, on average, than women who do not have a mutation, but the difference is small and does not appear to affect fertility.

South Asians comprise one of the fastest growing immigrant groups in North America. Evidence indicates that South Asian (SA) immigrant women are vulnerable to low rates of breast cancer screening. Yet, there is a dearth of knowledge pertaining to socioculturally tailored strategies to guide the uptake of screening mammography in the SA community. In 2010, the authors conducted semi-structured focus groups (FG) to elicit perspectives of health and social service professionals on possible solutions to barriers identified by SA immigrant women in a recent study conducted in the Greater Toronto Area. Thirty-five health and social services staff members participated in five FG. The discussions were audio taped and detailed field notes were taken. All collected data were transcribed verbatim and thematic analysis was conducted using techniques of constant comparison within and across the group discussions. Three dominant themes were identified: (i) 'Target and Tailor' focused on awareness raising through multiple direct and indirect modes or approaches with underlying shared processes of involving men and the whole family, use of first language and learning from peers; (ii) 'Enhancing Access to Services' included a focus on 'adding ancillary services' and 'reinforcement of existing services' including expansion to a one-stop model; and (iii) 'Meta-Characteristics' centred on providing 'multi-pronged' approaches to reach the community, and 'sustainability' of initiatives by addressing structural barriers of adequate funding, healthcare provider mix, inter-sectoral collaboration and community voice. The findings simultaneously shed light on the grassroot practical strategies and the system level changes to develop efficient programmes for the uptake of mammography among SA immigrant women. The parallel focus on the 'Target and Tailor' and 'Enhancing Access to Services' calls for co-ordination at the policy level so that multiple sectors work jointly to streamline resources, or meta-characteristics.

BACKGROUND: Germline mutations in BRCA1 and BRCA2 predispose to pancreatic cancer. We estimated the incidence of pancreatic cancer in a cohort of female carriers of BRCA1 and BRCA2 mutation. We also estimated survival rates in pancreatic cancer cases from families with a BRCA mutation. METHODS: We followed 5149 women with a mutation for new cases of pancreatic cancer. The standardised incidence ratios (SIR) for pancreatic cancer were calculated based on age group and country of residence. We also reviewed the pedigrees of 8140 pedigrees with a BRCA1 or a BRCA2 mutation for those with a case of pancreatic cancer. We recorded the year of diagnosis and the year of death for 351 identified cases. RESULTS: Eight incident pancreatic cancer cases were identified among all mutation carriers. The SIR for BRCA1 carriers was 2.55 (95% CI=1.03-5.31, P=0.04) and for BRCA2 carriers was 2.13 (95% CI=0.36-7.03, P=0.3). The 5-year survival rate was 5% for cases from a BRCA1 family and 4% for cases from a BRCA2 family. CONCLUSION: The risk of pancreatic cancer is approximately doubled in female BRCA carriers. The poor survival in familial pancreatic cancer underscores the need for novel anti-tumoural strategies.

It is well known that early-onset breast cancer may be due to an inherited predisposition. When evaluating women diagnosed with breast cancer under age 30, two important syndromes are typically considered: Hereditary Breast and Ovarian Cancer Syndrome and Li-Fraumeni syndrome. Many women are offered genetic testing for mutations in the BRCA1 and BRCA2 genes; however, few are offered genetic testing for mutations in the TP53 gene. There is a concern that overly restrictive testing of TP53 may fail to recognize families with Li-Fraumeni syndrome. We reviewed the genetic test results and family histories of all women with early-onset breast cancer who had genetic testing of the TP53 gene at the Toronto Hospital for Sick Children. Of the 28 women tested, six (33.3 %) had a mutation in the TP53 gene; a mutation was found in 7.7 % of women who did not meet current criteria for Li-Fraumeni syndrome. By reviewing similar data published between 2000 and 2011, we estimate that 5-8 % of women diagnosed with early-onset breast cancer, and who have a negative family history, may have a mutation in the TP53 gene. Given the potential benefits versus harms of this testing, we discuss the option of simultaneous testing of all three genes (BRCA1, BRCA2, and TP53) for women diagnosed with breast cancer before age 30.

BACKGROUND: The problems of cancer are increasing in low- and middle-income countries (LMCs), which now have significant majorities of the global case and mortality burdens. The professional oncology community is being increasingly called upon to define pragmatic and realistic approaches to these problems. PATIENTS AND METHODS: Focusing on mortality and case burden outcomes defines public health oncology or population-affecting cancer medicine. We use this focus to consider practical approaches. RESULTS: The greatest cancer burdens are in Asia. A public health oncology perspective mandates: first, addressing the major and social challenges of cancer medicine for populations: human rights, health systems, corruption, and our limited knowledge base for value-conscious interventions. Second, adoption of evolving concepts and models for sustainable development in LMCs. Third, clear and realistic statements of action and inaction affecting populations, grounded in our best cancer science, and attention to these. Finally, framing the goals and challenges for population-affecting cancer medicine requires a change in paradigm from historical top-down models of technology transfer, to one which is community-grounded and local-evidence based. CONCLUSION: Public health oncology perspectives define clear focus for much needed research on country-specific practical approaches to cancer control.