Hypothesis: Breast cancer gene (BRCA) mutation status affects patients' surgical decisions when genetic cancer risk assessment is offered at the time of breast cancer diagnosis, prior to definitive treatment. Patients and Interventions:Outcomes following genetic cancer risk assessment were studied for women newly diagnosed as having breast cancer who were prospectively enrolled in an institutional review boardapproved hereditary cancer registry during a 1-year sampling frame. BRCA gene analysis was offered to subjects with a calculated mutation probability of 10% or higher. Review of medical records and telephone survey were used to document surgical treatment decisions following genetic cancer risk assessment.Results: Thirty-seven of 233 women in the registry were enrolled at the time of a breast cancer diagnosis. The interval from diagnosis to genetic cancer risk assessment ranged from 3 to 60 days. The mean calculated probabil-ity of a BRCA gene mutation was 21% across the cohort. Two women were not tested because of low prior probabilities of mutation detection, and 3 declined owing to intercurrent psychological stressors. Of the remaining 32 patients, no BRCA gene mutation was detected in 22 (69%), 3 (9%) were found to carry a variant of uncertain significance, and 7 (22%) had a deleterious mutation. All 7 subjects with a deleterious mutation opted for bilateral mastectomy, whereas 20 of 22 patients with negative test results chose stage-appropriate treatment (PϽ.001).Conclusions: Genetic cancer risk assessment at the time of breast cancer diagnosis significantly affected women's treatment decisions. Although need and feasibility are demonstrated, the logistics of genetic cancer risk assessment during breast cancer diagnosis prove challenging.

BACKGROUND This report offers a unique analysis of the psychological distress associated with ovarian cancer in a review of natural correspondence between ovarian cancer survivors and an ovarian cancer newsletter. METHODS A review of 21,806 letters, cards, and e‐mails reflecting correspondence from January 1994 to December 2000 between ovarian cancer survivors and the founding editor of Conversations!: The International Newsletter for those Fighting Ovarian Cancer was performed using ethnographic qualitative research methods. Statements related to the impact of disease were bracketed and coded within physical, psychological, social, and spiritual domains according to the City of Hope Quality of Life Ovarian Cancer instrument. Statements that reflected psychological well being were then evaluated with respect to the disease trajectory (i.e., diagnosis, treatment, remission, recurrence, and advanced disease/end of life). RESULTS A total of 1282 communications were identified that pertained to psychological well being. Findings based on major themes derived from the analysis included descriptions of stressors associated with disease status. Significant stressors were identified within all phases of diagnosis, treatment, remission, and recurrence. Women described both positive and negative effects of disease and frequently demonstrated resourcefulness and perseverance by sharing coping mechanisms and survival strategies. CONCLUSIONS The natural correspondence from women with ovarian cancer provided a rare opportunity to capture the psychological concerns of women throughout all stages of the cancer trajectory. Health care professionals' awareness of the common psychological stressors throughout the ovarian cancer trajectory may allow them to identify more readily the needs for support, leading to improvement in overall quality of life. Cancer 2003;98:1061–71. © 2003 American Cancer Society. DOI 10.1002/cncr.11291

Early age at first birth and multiparity have been associated with a decrease in the risk of breast cancer in women in the general population. We examined whether this relationship is also present in women at high risk of breast cancer due to the presence of a mutation in either of the 2 breast cancer susceptibility genes, BRCA1 or BRCA2. We performed a matched case-control study of 1,260 pairs of women with known BRCA1 or BRCA2 mutations, recruited from North America, Europe and Israel. Women who had been diagnosed with breast cancer were matched with unaffected control subjects for year of birth, country of residence, and mutation (BRCA1 or BRCA2). Study subjects completed a questionnaire detailing their reproductive histories. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. Among BRCA1 carriers, parity per se was not associated with the risk of breast cancer (OR for parous vs. nulliparous 5 0.94; 95% CI 5 0.75-1.19; p 5 0.62). However, women with a BRCA1 mutation and 4 or more children had a 38% decrease in breast cancer risk compared to nulliparous women (OR 5 0.62; 95% CI 5 0.41-0.94). In contrast, among BRCA2 carriers, increasing parity was associated with an increased risk of breast cancer; women with 2 or more children were at approximately 1.5 times the risk of breast cancer as nulliparous women (OR 5 1.53; 95% CI 5 1.01-2.32; p 5 0.05). Among women with BRCA2 mutations and who were younger than age 50, the (adjusted) risk of breast cancer increased by 17% with each additional birth (OR 5 1.17; 95% CI 5 1.01-1.36; p 5 0.03). There was no significant increase in the risk of breast cancer among BRCA2 carriers older than 50 (OR for each additional birth 5 0.97; 95% CI 5 0.58-1.53; p 5 0.92). In the 2-year period following a birth, the risk of breast cancer in a BRCA2 carrier was increased by 70% compared to nulliparous controls (OR 5 1.70; 95% CI 5 0.97-3.0). There was a much smaller increase in breast cancer risk among BRCA2 carriers whose last birth was 5 or more years in the past (OR 5 1.24; 95% CI 5 0.79-1.95). A modest reduction in risk of breast cancer was observed among BRCA1 carriers with 4 or more births. Among BRCA2 carriers, increasing parity was associated with a significant increase in the risk of breast cancer before age 50 and this increase was greatest in the 2-year period following a pregnancy. ' 2005 Wiley-Liss, Inc.Key words: parity; breast cancer; BRCA mutation The lifetime risk of breast cancer among carriers of mutations in BRCA1 or BRCA2 is approximately 80%, 1,2 but individual risks may vary due to the effect of modifying factors.3 Reproductive factors have long been known to be important in the risk of breast cancer in the general population. 4 In an earlier study, we reported that increasing parity was associated with an increased risk of early-onset (< 40 year of age) breast cancer in both BRCA1 and BRCA2 carriers.5 However, the size of this study was small (189 matched pairs with BRCA1 mutations and 47 matched pairs with BRCA...

ERMLINE BRCA1 OR BRCA2 gene mutations significantly increase a woman's risk of breast cancer (50%-85%) and ovarian cancer (16%-50%). 1-5 Identifying women who have had BRCAassociated breast cancer is important because the risk of a new primary breast cancer within 10 years following initial diagnosis is as high as 40% in the absence of oophorectomy or tamoxifen treatment. 6 The corresponding 10-year risk of ovarian cancer is also substantial (6%-12%). 7 Limited-stage breast cancer patients who carry a BRCA gene mutation are offered the option of riskreducing mastectomy, and oophorectomy is recommended. 8,9 Documented efficacy of screening and risk reduction interventions provides evidence for individualized risk management advice, making genetic cancer risk assessment (GCRA) a component of medically necessary care. 10,11 Identifying appropriate candidates for GCRA is challenging. The general consensus (eg, American College of Medical Genetics, National Comprehensive Cancer Network 11-14) is that BRCA testing is not appropriate for unaffected women in the general population, but there is less clarity in this re-For editorial comment see p 2637.

This study describes the symptom experience of women with ovarian cancer. A body of data consisting of 21,806 letters, cards, and e-mails written by ovarian cancer patients was donated to the City of Hope investigators by the founder and editor of Conversations!: The International Newsletter for Those Fighting Ovarian Cancer. Using ethnographic qualitative research procedures, meaningful comments in the data were bracketed and coded within physical, psychological, social, and spiritual domains according to the City of Hope QOL-Ovarian Cancer instrument. Six hundred seventy-seven (677) comments were identified as pertaining to pre- and post-diagnostic symptomatology. Findings, based on major themes derived from the analysis, included distress over delayed diagnoses given the presence of pre-diagnosis symptoms. Frequently described post-diagnosis symptoms included pain, fatigue, gastrointestinal effects, and menstrual and fertility changes. Women demonstrated resourcefulness and optimism by sharing innovative ideas for coping with varied symptoms. Significant attention was dedicated to complementary and alternative therapies, both for symptom management and with curative intent. Findings demonstrate the need to improve diagnostic tests, symptom management, and patient education.