The predominant role of surgery in the prevention and new trends in the surgical treatment of women with BRCA1/2 mutations

Department of Surgery, Ioannina University School of Medicine, 45110, Ioannina, Greece.
Annals of Surgical Oncology (Impact Factor: 3.94). 02/2008; 15(1):21-33. DOI: 10.1245/s10434-007-9612-4
Source: PubMed

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.

  • Source
    [Show abstract] [Hide abstract]
    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
  • Source
    Hereditary Cancer in Clinical Practice 04/2012; 10(2). DOI:10.1186/1897-4287-10-S2-A54 · 1.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: With the better understanding of breast cancer history and biology, improved diagnostic modalities and the shift towards minimally invasive surgeries, indications for prophylactic mastectomy, skin sparing or skin reducing mastectomies (SSM/SRM) with nipple areolar complex (NAC) preservation coupled with immediate breast reconstruction are gaining popularity. The authors share their experience and conception with mastectomy and immediate alloplastic breast reconstruction with the esthetic circumvertical mammoplasty pattern combined with the dermal barrier buttress flap. Material and methods: The described technique was performed for 28 patients presenting for mastectomy and immediate alloplastic breast reconstruction. With close collaboration between the oncologic and plastic surgeons, mastectomy was performed in all cases with the esthetic circumvertical mammoplasty pattern. To achieve safe excision and optimal reconstruction, the standard incisions could be custom designed to fit oncologic requirements and allow the creation of a dermal barrier flap used as a buttress separating the implant from the suture line. Conclusion: The circumvertical mastectomy pattern combined with the dermal barrier buttress flap is a versatile option allowing safe reconstruction regardless of the tumor and necessary skin excision location.
    International Journal of Surgery (London, England) 08/2014; 12(10). DOI:10.1016/j.ijsu.2014.08.401 · 1.44 Impact Factor