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.
"Mutation carriers and their physicians often struggle with formulating an effective intervention strategy. Usual dilemmas include the choice of preventive surgeries, the age at which to undergo a chosen surgery, and whether or not to screen in any given year  .The choice of intervention actions is guided by the following: increased survival, reduced incidence of breast and ovarian cancers, quality-adjusted life years, increased probability of death from other causes, and the costs and other undesirable consequences of intervention actions and treatment. "
[Show abstract][Hide abstract] ABSTRACT: Purpose:
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 between the ages of 30 and 65 and any prior intervention history.
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.
The results from MDP model show that for 30-year-old women with BRCA1 mutation and no prior intervention history, the cost-optimal 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 at 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 cost-optimal strategies offer near maximum survival rate and near minimum cancer incidence rates by age 70, when compared to other ad hoc strategies.
"Prevention and prediction of LR and RR at the time of initial diagnosis of primary tumor might be an important issue if LR and RR, as the first event after BCT, influences DRFS and OS. Patients at high risk for LR and RR can benefit from initial aggressive surgery , but, no robust marker predicts the risk of locoregional failure, which would be helpful when selecting an ideal initial therapy . A major effort is underway to predict LR and RR using molecular markers in genome-wide association studies. "
[Show abstract][Hide abstract] 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.
"Since then, PO has reduced the risk of ovarian cancer by more than 50% in these patients. In the absence of reliable methods for the early detection of ovarian cancer, PO has been proposed as the most effective way to prevent this potentially lethal disease in this high-risk group of women  . Although PO is effective in preventing breast and ovarian cancer, there seems to be a higher mortality for premenopausal oophorectomy, and these high-risk women are not candidates for hormone replacement therapy because of their increased Address all correspondence to: "
[Show abstract][Hide abstract] ABSTRACT: Currently, there is no adequate technology to detect early stage ovarian cancers. Most of the cancers in the ovary are detected when the cancer has already metastasized to other parts of the body. As a result, ovarian cancer has the highest mortality of all gynecologic cancers with a 5-year survival rate of 30% or less. Thus, there is an urgent need to improve the current diagnostic techniques. Photoacoustic imaging (PAI) is an emerging modality with a great potential to assist ultrasound for detecting ovarian cancer noninvasively. In this article, we report the first study of coregistered ultrasound and PAI of 33 ex vivo human ovaries. An assessment of the photoacoustic images has revealed light absorption distribution in the ovary, which is directly related to the vasculature distribution and amount. Quantification of the light absorption levels in the ovary has indicated that, in the postmenopausal group, malignant ovaries showed significantly higher light absorption than normal ones (P = .0237). For these two groups, we have obtained a sensitivity of 83% and a specificity of 83%. This result suggests that PAI is a promising modality for improving ultrasound diagnosis of ovarian cancer.
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