The predominant role of surgery in the prevention and new trends in the surgical treatment of women with BRCA1/2 mutations
ABSTRACT Advances in understanding molecular and genetic mechanisms underlying cancer promise an "individualized" management of the disease. Women with a BRCA1 or BRCA2 germ-line mutation are at very high risk of breast and/or ovarian cancer. Because high-quality data are lacking from randomized trials, prevention strategies and treatment of patients with BRCA-associated breast cancer are complex.
The data for this review were obtained by searching PubMed and Medline for articles about optimizing prevention and treating women with familial susceptibility to breast and ovarian cancer.
Prophylactic surgery is the rational approach for women who carry the BRCA mutation; chemoprevention and/or intensified surveillance represent alternative approaches. Prophylactic bilateral salpingo-oophorectomy is superior to bilateral prophylactic mastectomy. However, reaching a definitive clinical decision is complex, and several variables should be considered for an individualized approach. Accumulating data support the concept of more extensive surgery for newly diagnosed breast cancer in women with a BRCA mutation but new unbaised studies are needed for an evidence-based approach . Such patients treated with breast conservation therapy for early-stage breast cancer are at higher risk of contralateral breast cancer than noncarriers. Primary bilateral mastectomy could also be considered and discussed with these patients. Breast tumors from BRCA1 mutation carriers are predominantly of basal subtype (i.e., triple negative), and BRCA2 mutation carriers are of luminal subtype (i.e., estrogen receptor positive). Decisions on adjuvant treatment are based on estrogen receptor, progesterone receptor, and HER2 status.
The complex management of healthy women and breast cancer patients with familial susceptibility to breast and ovarian cancer requires an individualized prevention or treatment strategy by an experienced team.
- SourceAvailable from: Dimosthenis ZiogasRadiotherapy and Oncology 04/2008; 90(1):161-2. DOI:10.1016/j.radonc.2008.02.020 · 4.86 Impact Factor
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ABSTRACT: Women with BRCA1/2 mutations have higher risk for breast and ovarian cancers. Available intervention actions include prophylactic surgeries and breast screening, which vary significantly in cost, cancer prevention, and in resulting death from other causes. We present a model designed to yield optimal intervention strategies for mutation carriers with age between 30 and 65 and any prior intervention history. Methods A Markov decision process (MDP) model is developed that considers yearly state transitions for the mutation carriers and state dependent intervention actions. State is defined as a vector comprising mutation type, health states, prior intervention actions, and age. A discounted value iteration algorithm is used to obtain optimal strategies from the MDP model using both cost and quality-adjusted life years (QALYs) as rewards. Results The results from MDP model show that for 30 year old women with BRCA1 mutation and no prior intervention history, the costoptimal strategy is a combination of prophylactic mastectomy (PM) and prophylactic oophorectomy (PO) at age 30 with no screening afterwards. Whereas, the QALYs-optimal strategy suggests PO at age 30 and PM at age 50 with screening afterwards. For BRCA2 mutation carriers of age 30, the cost-optimal strategy is PO at age 30, PM at age 40, and yearly screening only after age 56. Corresponding QALYs-optimal strategy is PM at age 40 with screening. Strategies for all other ages (31 to 65) are obtained and presented. It is also demonstrated that the costoptimal strategies offer near maximum survival rate and near minimum cancer incidence rates by age 70, when compared to other ad hoc strategies.04/2014; 19(2). DOI:10.1109/JBHI.2014.2319246
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ABSTRACT: We evaluated the effect of local recurrence (LR) and regional recurrence (RR) on distant metastasis and survival in patients treated with breast conservation therapy (BCT). We analyzed 907 patients who were treated for invasive breast cancer between 1993 and 2006. With 53 months of follow-up, 28 patients (3.1%) developed LR in the breast and 12 patients (1.3%) developed RR before distant metastasis. LR and RR were separated into four patterns to determine the prognostic relevance of recurrence site and time to recurrence: LR within 3 years (early LR), LR after 3 years (late LR), RR within 3 years (early RR), and RR after 3 years (late RR). Early LR (hazard ratio [HR], 4.76; p=0.003) and early RR (HR, 18.16; p<0.001) were independent predictors of distant metastasis. In terms of overall survival, early LR (HR, 5.24; p=0.002), and early RR (HR, 18.80; p<0.001) were significantly related with poor survival. Patients with late LR/RR had a similar favorable prognosis compared with patients who never experienced LR/RR. The result suggests that time to LR/RR following BCT is a significant predictor developing a distant metastasis and surviving.09/2011; 14(3):191-7. DOI:10.4048/jbc.2011.14.3.191