Purpose: The purposes of this study were to estimate the reduction in risk of ovarian, fallopian tube, or peritoneal cancer in women with a BRCA1 or BRCA2 mutation after oophorectomy, by age of oophorectomy; to estimate the impact of prophylactic oophorectomy on all-cause mortality; and to estimate 5-year survival associated with clinically detected ovarian, occult, and peritoneal cancers diagnosed in the cohort. Patients and Methods: Women with a BRCA1 or BRCA2 mutation were identified from an international registry; 5,783 women completed a baseline questionnaire and ≥ one follow-up questionnaires. Women were observed until either diagnosis of ovarian, fallopian tube, or peritoneal cancer, death, or date of most recent follow-up. Hazard ratios (HRs) for cancer incidence and all-cause mortality associated with oophorectomy were evaluated using time-dependent survival analyses. Results: After an average follow-up period of 5.6 years, 186 women developed either ovarian (n = 132), fallopian (n = 22), or peritoneal (n = 32) cancer, of whom 68 have died. HR for ovarian, fallopian, or peritoneal cancer associated with bilateral oophorectomy was 0.20 (95% CI, 0.13 to 0.30; P < .001). Among women who had no history of cancer at baseline, HR for all-cause mortality to age 70 years associated with an oophorectomy was 0.23 (95% CI, 0.13 to 0.39; P < .001). Conclusion: Preventive oophorectomy was associated with an 80% reduction in the risk of ovarian, fallopian tube, or peritoneal cancer in BRCA1 or BRCA2 carriers and a 77% reduction in all-cause mortality.

In the United States, incidence rates of breast cancer among women vary substantially by racial/ethnic group.^1-3 The age-adjusted rates for breast cancer are 129 per 100 000 for non-Hispanic white women, 93 per 100 000 for Hispanic women, 123 per 100 000 for black women, and 94 per 100 000 for Asian women.¹ There are differences in survival as well; crude 10-year survival rates are 80% for white women, 78% for Hispanic American women, 66% for black women, and 82% for Asian women.⁴

Ovarian cancer is the second most lethal gynecological malignancy. The tumour biomarker CA125 has been used as the primary ovarian cancer marker for the past four decades. The focus on diagnosing ovarian cancer in stages I and II using CA125 as a diagnostic biomarker has not improved patients’ survival. Therefore, screening average-risk asymptomatic women with CA125 is not recommended by any professional society. The dualistic model of ovarian cancer carcinogenesis suggests that type II tumours are responsible for the majority of ovarian cancer mortality. However, type II tumours are rarely diagnosed in stages I and II. The recent shift of focus to the diagnosis of low volume type II ovarian cancer in its early stages of evolution provides a new and valuable target for screening. Type II ovarian cancers are usually diagnosed in advanced stages and have significantly higher CA125 levels than type I tumours. The detection of low volume type II carcinomas in stage IIIa/b is associated with a higher likelihood for optimal cytoreduction, the most robust prognostic indicator for ovarian cancer patients. The diagnosis of type II ovarian cancer in the early substages of stage III with CA125 may be possible using a higher cutoff point rather than the traditionally used 35 U/mL through the use of point-of-care CA125 assays in primary care facilities. Rapid point-of-care testing also has the potential for effective longitudinal screening and quick monitoring of ovarian cancer patients during and after treatment. This review covers the role of CA125 in the diagnosis and management of ovarian cancer and explores novel and more effective screening strategies with CA125.

Research from JAMA Oncology — Breast Cancer Mortality After a Diagnosis of Ductal Carcinoma In Situ

Several options for cancer prevention are available for women with a BRCA1 or BRCA2 mutation, including prophylactic surgery, chemoprevention and screening. The authors report on preventive practices in women with mutations from 9 countries and examine differences in uptake according to country. Women with a BRCA1 or BRCA2 mutation were contacted after receiving their genetic test result and were questioned regarding their preventive practices. Information was recorded on prophylactic mastectomy, prophylactic oophorectomy, use of tamoxifen and screening (MRI and mammography). Two thousand six hundred seventy‐seven women with a BRCA1 or BRCA2 mutation from 9 countries were included. The follow‐up questionnaire was completed a mean of 3.9 years (range 1.5–10.3 years) after genetic testing. One thousand five hundred thirty‐one women (57.2%) had a bilateral prophylactic oophorectomy. Of the 1,383 women without breast cancer, 248 (18.0%) had had a prophylactic bilateral mastectomy. Among those who did not have a prophylactic mastectomy, only 76 women (5.5%) took tamoxifen and 40 women (2.9%) took raloxifene for breast cancer prevention. Approximately one‐half of the women at risk for breast cancer had taken no preventive option, relying solely on screening. There were large differences in the uptake of the different preventive options by country of residence. Prophylactic oophorectomy is now generally accepted by women and their physicians as a cancer preventive measure. However, only the minority of women with a BRCA1 or BRCA2 mutation opt for prophylactic mastectomy or take tamoxifen for the prevention of hereditary breast cancer. Approximately one‐half of women at risk for breast cancer rely on screening alone.