Anxiety and Depression in Young Women With Metastatic Breast Cancer: A Cross-Sectional Study.

BACKGROUND: Young adults with cancer experience disruptions in their normal developmental trajectories and commonly experience psychologic distress related to their diagnoses. Young women with metastatic breast cancer (MBC) are at particular risk of adverse mental health outcomes. OBJECTIVE: We sought to determine the prevalence of and factors associated with anxiety and depression symptoms in young women with newly diagnosed de novo MBC. METHODS: A total of 54 women with newly diagnosed de novo MBC were identified from an ongoing, prospective, multicenter cohort of women diagnosed with breast cancer at age <40. Depression and anxiety symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS). Items assessing socio-demographics, physical symptom burden, social support, and disease and treatment history, with complementary medical record review, were used to assess variables potentially associated with anxiety and depression symptoms. RESULTS: Mean HADS Depression score was 4.4 (standard deviation = 3.7) and mean HADS Anxiety score was 7.9 (standard deviation = 5.0). Eleven (20%) women scored ≥8 on the HADS Depression subscale, the suggested threshold for depression/anxiety screening, and 24 (44%) women scored ≥8 on the HADS Anxiety subscale. In a multivariable model of anxiety, higher physical symptom scores (odds ratio = 4.41, p = 0.005) was significantly associated with higher anxiety scores. None of the other variables improved the model fit. CONCLUSION: In this study, a considerable proportion of young women with newly diagnosed MBC experienced anxiety symptoms, although depression was less common. Future strategies focused on distress reduction in young MBC patients should focus on physical symptom management as well as anxiety identification and management.

Oncology Physicians' Perspectives on Practices and Barriers to Fertility Preservation and the Feasibility of a Prospective Study of Pregnancy After Breast Cancer.

PURPOSE: POSITIVE (Pregnancy Outcome and Safety of Interrupting Therapy for women with endocrine responsIVE breast cancer) is a prospective clinical trial assessing safety and pregnancy outcomes in premenopausal hormone receptor-positive breast cancer survivors (age ≤42) who interrupt endocrine therapy (ET) to attempt pregnancy. We sought to assess interest in this study and perspectives on fertility preservation (FP) among United States medical oncologists who had previously enrolled women at their institutions on select premenopausal endocrine studies. METHODS: From August 2015 to December 2015, 301 investigators were invited to complete a web-based survey on behalf of their institution. We assessed FP practices and attitudes, barriers to discussing FP, and willingness to open/enroll women on POSITIVE. RESULTS: Of 93 respondents (31%), most were affiliated with an National Cancer Institute (NCI)-designated comprehensive cancer center (44%). Almost all said they usually or always discussed the issue of future fertility with patients (98%) and referred patients with fertility questions to specialists (97%). Over half of respondents cited discomfort with recommending women to stop ET, as well as perceived patient concern regarding ET interruption, as factors seen as influencing POSITIVE enrollment; however, 84% were willing to recommend trial participation for selected patients. CONCLUSIONS: Most providers reported discussing fertility with their young patients, indicating awareness of FP guidelines for cancer patients. While most oncologists said that they would be willing to recommend POSITIVE, many also expressed discomfort in endorsing women to stop ET temporarily, underscoring the need for prospective data regarding the safety of ET interruption. High willingness to recommend POSITIVE suggests the potential for successful accrual to this study, which addresses a critical issue for young breast cancer survivors.

BRCA1 and BRCA2 Mutation Testing in Young Women With Breast Cancer.

IMPORTANCE: BRCA testing is recommended for young women diagnosed as having breast cancer, but little is known about decisions surrounding testing and how results may influence treatment decisions in young patients. OBJECTIVES: To describe the use of BRCA testing and to evaluate how concerns about genetic risk and use of genetic information affect subsequent treatment decisions in young women with breast cancer. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis of data collected following the opening of the study to accrual from October 10, 2006, through December 31, 2014, as part of the Helping Ourselves, Helping Others: Young Women's Breast Cancer Study, an ongoing prospective cohort study. Study participants included 897 women aged 40 years and younger at breast cancer diagnosis from 11 academic and community medical centers. MAIN OUTCOMES AND MEASURES: Frequency and trends in the use of BRCA testing and how genetic information is used to make treatment decisions among women who test positive vs negative for a BRCA mutation. RESULTS: A total of 780 (87.0%) of 897 women reported BRCA testing by 1 year after breast cancer diagnosis (mean age at diagnosis, 35.3 vs 36.9 years for untested women; P < .001), with the frequency of testing increasing among women diagnosed from August 1, 2006, through December 31, 2013. Of 39 women who were diagnosed as having breast cancer in 2006, 30 (76.9%) reported testing. In 2007, a slightly lower percentage of women (87 of 124 [70.2%]) reported testing; however, the proportion tested increased each subsequent year, with 141 (96.6%) of 146 and 123 (95.3%) of 129 women diagnosed as having breast cancer in 2012 and 2013, respectively, reporting BRCA testing (P < .001). Among untested women, 37 (31.6%) of 117 did not report discussion of the possibility that they might have a mutation with a physician and/or genetic counselor, and 43 (36.8%) of 117 were thinking of testing in the future. A total of 248 (29.8%) of 831 women said that knowledge or concern about genetic risk influenced treatment decisions; among these women, 76 (86.4%) of 88 mutation carriers and 82 (51.2%) of 160 noncarriers chose bilateral mastectomy (P < .001). Fewer women reported that systemic treatment decisions were influenced by genetic risk concern. CONCLUSIONS AND RELEVANCE: Rates of BRCA1 and BRCA2 mutation testing are increasing in young women with breast cancer. Given that knowledge and concern about genetic risk influence surgical decisions and may affect systemic therapy trial eligibility, all young women with breast cancer should be counseled and offered genetic testing, consistent with the National Comprehensive Cancer Network guidelines.

Pregnancy-specific association of vitamin D deficiency and bacterial vaginosis.

OBJECTIVE: Recent data suggest vitamin D deficiency (VDD) is associated with bacterial vaginosis (BV) during pregnancy. We hypothesized that VDD is a risk factor for BV in nonpregnant women. STUDY DESIGN: Using National Health and Nutrition Examination Survey data, we conducted multivariable logistic regression analyses stratified by pregnancy. RESULTS: VDD was associated with BV only in pregnant women (adjusted odds ratio [AOR], 2.87; 95% confidence interval [CI], 1.13-7.28). Among nonpregnant women, douching (AOR, 1.72; 95% CI, 1.25-2.37), smoking (AOR, 1.66; 95% CI, 1.23-2.24), and black race (AOR, 2.41; 95% CI, 1.67-3.47) were associated with BV; oral contraceptive use was inversely associated with BV (AOR, 0.60; 95% CI, 0.40-0.90). VDD moderated the association between smoking and BV in nonpregnant women. CONCLUSION: Risk factors for BV differ by pregnancy status. VDD was a modifiable risk factor for BV among pregnant women; evaluation of vitamin D supplementation for prevention or adjunct therapy of BV in pregnancy is warranted.

Inappropriate use of vancomycin for preventing perinatal group B streptococcal (GBS) disease in laboring patients.

OBJECTIVE: The 2002 CDC guidelines for the prevention of perinatal group B streptococcus (GBS) stipulate that vancomycin is reserved for penicillin-allergic women at high risk for beta-lactam anaphylaxis with resistance to clindamycin or erythromycin. Our objective was to evaluate practitioner adherence to these guidelines. METHODS: This is a retrospective chart review of patients admitted to labor and delivery who received vancomycin for GBS prophylaxis from January 1st, 2005 to June 1st, 2007. Identification and documentation of allergic reactions to beta lactams and performance of GBS sensitivities at the time of screening were recorded. RESULTS: Eighty-seven patients reporting a penicillin allergy received vancomycin during labor. In 71 patients screened at 35-37 weeks, sensitivities were not performed for 55 patients, of which 10 reported an anaphylactic-like reaction to penicillin. Of 15 patients who had sensitivities performed at the time of screening and were resistant to clindamycin and/or erythromycin, only two patients, however, described an anaphylactic-like reaction to penicillin. Fourteen patients received vancomycin due to an unknown GBS status at <35 weeks of gestation and only three patients from this group reported an anaphylactic-like reaction to penicillin. There were deviations from the CDC protocol in 82 (94%) of 87 patients who received intrapartum vancomycin there were deviations in the CDC protocol. CONCLUSION: Most patients receiving intrapartum vancomycin for perinatal GBS prophylaxis either did not have a culture with sensitivities performed at the time of GBS screening due to a history of anaphylactic-like reactions to penicillin or received vancomycin for a mild or unknown allergy. Physician adherence to the CDC guidelines with regards to the use of vancomycin is far from optimal.

Is adjuvant chemotherapy of benefit for postmenopausal women who receive endocrine treatment for highly endocrine-responsive, node-positive breast cancer? International Breast Cancer Study Group Trials VII and 12-93.

To compare the efficacy of chemoendocrine treatment with that of endocrine treatment (ET) alone for postmenopausal women with highly endocrine responsive breast cancer. In the International Breast Cancer Study Group (IBCSG) Trials VII and 12-93, postmenopausal women with node-positive, estrogen receptor (ER)-positive or ER-negative, operable breast cancer were randomized to receive either chemotherapy or endocrine therapy or combined chemoendocrine treatment. Results were analyzed overall in the cohort of 893 patients with endocrine-responsive disease, and according to prospectively defined categories of ER, age and nodal status. STEPP analyses assessed chemotherapy effect. The median follow-up was 13 years. Adding chemotherapy reduced the relative risk of a disease-free survival event by 19% (P = 0.02) compared with ET alone. STEPP analyses showed little effect of chemotherapy for tumors with high levels of ER expression (P = 0.07), or for the cohort with one positive node (P = 0.03). Chemotherapy significantly improves disease-free survival for postmenopausal women with endocrine-responsive breast cancer, but the magnitude of the effect is substantially attenuated if ER levels are high.

Age of menopause among women who remain premenopausal following treatment for early breast cancer: long-term results from International Breast Cancer Study Group Trials V and VI.

BACKGROUND: The likelihood of premature menopause has not been thoroughly explored in women who remain premenopausal after adjuvant chemotherapy for breast cancer. METHODS: We used data from the International Breast Cancer Study Group (IBCSG) Trials V and VI. Trial V enrolled 1407 eligible premenopausal women randomised to no systemic therapy (No CT) or 1 cycle of perioperative CMF-based chemotherapy (PeCT) if node negative, and 6 cycles of CMF-based chemotherapy postoperatively (CMFx6) or 1 cycle perioperative CMF-based chemotherapy plus CMFx6 postoperatively (CMFx7) if node positive. From Trial VI (a 2x2 factorial designed study of 3 versus 6 initial cycles of CMF and a reintroduction of three additional courses of CMF), we included 375 women randomised to receive only six initial cycles of CMF (CMFx6). FINDINGS: We excluded women who reported no menses during 12-24 months after randomisation (N=934), hysterectomy (N=16) or bilateral oophorectomy (N=8), or missing menses data (N=57), creating a cohort of 767 women; 540 women had been randomised to PeCT or no CT, 227 randomised to CMFx6 or 7. A Cox proportional hazards model revealed that CMFx6 or 7 (HR=2.03, p<0.0001) and temporary amenorrhea (HR=1.96, p<0.0001) were associated with premature menopause. INTERPRETATION: Women who remain premenopausal after 6 or 7 cycles of CMF-based chemotherapy have a higher likelihood of going through menopause at an earlier age than women who received little or no chemotherapy. Temporary cessation of menses appears to be a marker for earlier onset of menopause. These findings may assist women and clinicians when making treatment and reproductive decisions after a diagnosis of breast cancer.

Effects of a treatment gap during adjuvant chemotherapy in node-positive breast cancer: results of International Breast Cancer Study Group (IBCSG) Trials 13-93 and 14-93.

BACKGROUND: The International Breast Cancer Study Group (IBCSG) conducted two complementary randomized trials to assess whether a treatment-free gap during adjuvant chemotherapy influenced outcome. PATIENTS AND METHODS: From 1993 to 1999, IBCSG Trials 13-93 and 14-93 enrolled 2215 premenopausal and postmenopausal women with axillary node-positive, operable breast cancer. All patients received cyclophosphamide (Cytoxan, C) plus either doxorubicin (Adriamycin, A) or epirubicin (E) for four courses followed immediately (No Gap) or after a 16-week delay (Gap) by classical cyclophosphamide, methotrexate, and fluorouracil (CMF) for three courses. The median follow-up was 7.7 years. RESULTS: The Gap and No-Gap groups had similar disease-free survival (DFS) and overall survival (OS). No identified subgroup showed a statistically significant difference, but exploratory subgroup analysis noted a trend towards decreased DFS for Gap compared with No Gap for women with estrogen receptor (ER)-negative tumors not receiving tamoxifen, especially evident during the first 2 years. CONCLUSIONS: A 16-week gap between adjuvant AC/EC and CMF provided no benefit and may have increased early recurrence rates in patients with ER-negative tumors.

Toremifene and tamoxifen are equally effective for early-stage breast cancer: first results of International Breast Cancer Study Group Trials 12-93 and 14-93.

BACKGROUND: Toremifene is a chlorinated derivative of tamoxifen, developed to improve its risk-benefit profile. The International Breast Cancer Study Group (IBCSG) conducted two complementary randomized trials for peri- and postmenopausal patients with node-positive breast cancer to compare toremifene versus tamoxifen as the endocrine agent and simultaneously investigate a chemotherapy-oriented question. This is the first report of the endocrine comparison after a median follow-up of 5.5 years. PATIENTS AND METHODS: 1035 patients were available for analysis: 75% had estrogen receptor (ER)-positive primary tumors, the median number of involved axillary lymph nodes was three and 81% received prior adjuvant chemotherapy. RESULTS: Toremifene and tamoxifen yielded similar disease-free (DFS) and overall survival (OS): 5-year DFS rates of 72% and 69%, respectively [risk ratio (RR)=0.95; 95% confidence interval (CI)=0.76-1.18]; 5-year OS rates of 85% and 81%, respectively (RR = 1.03; 95% CI = 0.78-1.36). Similar outcomes were observed in the ER-positive cohort. Toxicities were similar in the two treatment groups with very few women (<1%) experiencing severe thromboembolic or cerebrovascular complications. Quality of life results were also similar. Nine patients developed early stage endometrial cancer (toremifene, six; tamoxifen, three). CONCLUSIONS: Toremifene is a valid and safe alternative to tamoxifen in postmenopausal women with endocrine-responsive breast cancer.