E10. Issues around hereditary breast cancer and local treatment

Abstract

Women with inherited germline BRCA1 (familial breast/ ovarian cancer gene 1) or BRCA2 (BRCA1/2) mutations have approximately a 55−85% cumulative risk of developing breast cancer by the age of 70. Knowledge of expected outcomes for BRCA1/2 mutation carriers following various breast cancer treatments is needed for decision-making [1,2]. The treatment goals for a woman with a BRCA-associated breast cancer should be to prevent recurrence of the initial cancer and to prevent second primary breast and ovarian cancers. Riskreduction interventions for BRCA-related breast cancer are relevant not only for clinical decisions in breast cancer patients but also for healthy subjects who are potential candidates for undergoing similar interventions. The literature on the impact of different surgical options and adjuvant systemic approaches aimed towards risk reduction for recurrences of ipsilateral and contralateral breast cancer will be reviewed. Breast-conserving therapy (BCT), defined as surgical excision and radiotherapy (RT), has been shown in multiple trials to result in comparable rates of tumour control and survival as mastectomy in women with sporadic early-stage disease. There are only limited data comparing outcomes following BCT versus mastectomy exclusively in women with known BRCA1/2 mutations. Estimates of local recurrence and contralateral new breast cancers following BCT compared with mastectomy could aid in surgical decision-making in a BRCA1/2 mutation carrier newly diagnosed with breast cancer. Pierce et al. [3] compared the clinical outcomes in women with BRCA1/2 mutations treated with BCT to outcomes in similarly staged BRCA1/2 mutation carriers treated with mastectomy. This study included 655 patients with BRCA1/2 mutations, and had a median follow-up of 8.2 years for BCT and 8.9 years for mastectomy. BRCA1/2 mutation carriers with breast cancer have similar survival rates whether treated with mastectomy or BCT. However, women undergoing BCT have an elevated risk of a second in-breast event that is significantly reduced with chemotherapy. Contralateral breast cancer events are very common. From this study we can conclude that breast-conserving surgery is associated with a higher probability of local recurrence, but is counterbalanced by effectiveness of chemotherapy in reducing this risk. Consistent support for the hypothesis that anti-oestrogens are effective in reducing contralateral breast cancer risks is available from the literature. On the other hand, data on chemoprevention approaches for healthy subjects are too preliminary to draw any conclusions from. Studies including conventional and newer hormonal drugs are needed to demonstrate the benefit of chemoprevention approaches. These may also deepen our knowledge on possible differences in the likelihood of clinical benefit to be expected among BRCA1/2-altered tumours. Assessment of long-term risks of ipsilateral [4] and both ipsilateral and contralateral [5] breast cancer have been studied. These studies led to the conclusion that patients with germline mutations have high risks for second primary tumours, although local recurrence rates were not statistically different. The rate of contralateral breast cancer is significantly higher in mutation carriers, which is why prophylactic surgery of the contralateral breast is a treatment option that needs to be discussed with the patient. Kirova et al. [6,7] investigated, after long-term follow-up, whether mutation status influenced the rate of ipsilateral and contralateral breast cancers after BCT. BRCA1 and BRCA2 genes were screened for germline mutations in 131 patients with a family history of breast and/or ovarian cancer who had undergone