Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory disease. We observed several molecular events associated with acquired resistance, including multiple independent reversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an alteration in molecular subtype, and recurrent promoter fusion associated with overexpression of the drug efflux pump MDR1.

This study examined the use of complementary and alternative medicine (CAM) therapies by breast cancer patients and the communication of their CAM use to their physicians relative to lymphedema symptoms and other factors. Breast cancer patients ( N = 148) in the State of Vermont were interviewed 2-3 years after their primary surgery using computer-aided telephone interviewing methods. Questionnaire items included demographic information, treatment, CAM use, lymphedema symptoms, and other measures. A large proportion (72.3%) reported using at least one CAM treatment after surgery. The most frequently used treatments were vitamins and nonfood supplements (72.3%), with herbal treatments, meditation, and traditional massage each being reported by about one-fifth of the women. Age, education, adjuvant chemotherapy, and extremity swelling were associated with use of more CAM treatments in a regression model. A large proportion (73.8%) of CAM users reported their CAM use to their physicians. Correlations between patients' income, adjuvant radiation therapy, and adjuvant tamoxifen use with communication of CAM use to their physicians were sought in a logistic regression model. CAM use is high among breast cancer patients in Vermont, and the number of CAM therapies used is related to demographic factors, adjuvant treatment, and lymphedema symptoms. Communication of CAM use to physicians appears to be multifaceted.

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Our study highlights two important areas of future research that could reduce the incidence of lymphedema. There is a need to better understand the role that treatment for high blood pressure may play in protecting women from arm edema. Second, the potential effect of weight as a modifiable lymphedema risk factor needs to be studied in more detail in light of the conflicting results of different studies.