Development and perception of surgery-specific goals of care discussions in the preoperative setting: A learning pilot.

BACKGROUND: Goals of care discussions are infrequently documented in the preoperative period. Furthermore, documentation does not consistently address what matters most to patients, although patient values (PV) are central to person-centered care. METHODS: A multidisciplinary working group was formed. An electronic note comprised of (1) topics of discussion, (2) PV, and (3) advance care planning (ACP), was created and embedded into existing note templates for Gynecologic Surgical Oncology. Surgeons and advanced practice providers (APPs) were educated to conduct and document these conversations in preoperative clinic for patients undergoing cancer surgery for a pilot period. Data were collected regarding usage of the template. Focus groups with surgeons, APPs, and patients were conducted. Qualitative analysis was performed on transcripts. RESULTS: During the pilot, 7 surgeon/APP teams utilized the template on a total of 55 notes. Average number of notes completed per surgeon was 7.8 (SD 8.5). Forty-six notes (84%) included topics of discussion, 15 (27%) included PV, 4 (7%) included ACP. Qualitative analysis of focus group transcripts revealed that clinicians and patients perceived the initiative to be useful and important, although implementation barriers were identified. CONCLUSION: Creating a surgery-specific GOC template is feasible. Iterative revisions are needed to increase utility in clinic workflows.

A single-arm, prospective trial investigating the effectiveness of a non-hormonal vaginal moisturizer containing hyaluronic acid in postmenopausal cancer survivors.

PURPOSE: To assess the feasibility and efficacy of a non-hormonal hyaluronic acid (HLA) vaginal gel in improving vulvovaginal estrogen-deprivation symptoms in postmenopausal women with a history of hormone receptor-positive (HR+) cancer. METHODS: For this single-arm, prospective longitudinal trial, we identified disease-free patients with a history of HR+ breast cancer treated with aromatase inhibitors or HR+ endometrial cancer treated with surgery and postoperative radiation. Participants used HLA daily for the first 2 weeks, and then 3×/week until weeks 12-14; dosage was then increased to 5×/week for non-responders. Vulvovaginal symptoms and pH were assessed at 4 time points (baseline [T1], 4-6 weeks [T2], 12-14 weeks [T3], 22-24 weeks [T4]) with clinical evaluation, the Vaginal Assessment Scale (VAS), Vulvar Assessment Scale (VuAS), Female Sexual Function Index (FSFI), and Menopausal Symptom Checklist (MSCL). RESULTS: Of 101 patients, mean age was 55 years (range, 31-78), 68% (n = 69) were partnered, and 60% (n = 61) were sexually active. In linear mixed models, VAS/VuAS scores significantly improved at all assessment points (all p < 0.001). MSCL scores similarly improved (all p < 0.001). FSFI scores significantly improved from T1 to T2 (p < 0.03), T3 (p < 0.001), and T4 (p < 0.001). Severe vaginal pH (> 6.5) decreased from 26% at T1 to 19% at T4 (p = 0.18). CONCLUSIONS: HLA moisturization improved vulvovaginal health/sexual function of cancer survivors. While HLA administration 1-2×/week is recommended for women in natural menopause, a 3-5×/week schedule appears to be more effective for symptom relief in cancer survivors.

Surgical ovarian suppression for adjuvant treatment in hormone receptor positive breast cancer in premenopausal patients.

OBJECTIVE: Ovarian suppression is recommended to complement endocrine therapy in premenopausal women with breast cancer and high-risk features. It can be achieved by either medical ovarian suppression or therapeutic bilateral salpingo-oophorectomy. Our objective was to evaluate characteristics of patients with stage I-III hormone receptor positive primary breast cancer who underwent bilateral salpingo-oophorectomy at our institution. MATERIALS AND METHODS: Premenopausal women with stage I-III hormone receptor positive primary breast cancer diagnosed between January 2010 and December 2014 were identified from a database. Patients with confirmed BRCA1/2 mutations were excluded. Distribution of characteristics between treatment groups was assessed using χ2 test and univariate logistic regression. A multivariate model was based on factors significant on univariate analysis. RESULTS: Of 2740 women identified, 2018 (74%) received endocrine treatment without ovarian ablation, 516 (19%) received endocrine treatment plus ovarian ablation, and 206 (7.5%) did not receive endocrine treatment. Among patients undergoing ovarian ablation 282/516 (55%) received medical ovarian suppression, while 234 (45%) underwent bilateral salpingo-oophorectomy. By univariate logistic analyses, predictors for ovarian ablation were younger age (OR 0.97), histology (other vs ductal: OR 0.23), lymph node involvement (OR 1.89), higher International Federation of Gynecology and Obstetrics (FIGO) stage (stage II vs I: OR 1.48; stage III vs I: OR 2.86), higher grade (grade 3 vs 1: OR 3.41; grade 2 vs 1: OR 2.99), chemotherapy (OR 1.52), and more recent year of diagnosis (2014 vs 2010; OR 1.713). Only year of diagnosis, stage, and human epidermal growth factor receptor 2 (HER-2) treatment remained significant in the multivariate model. Within the cohort undergoing ovarian ablation, older age (OR 1.05) was associated with therapeutic bilateral salpingo-oophorectomy. Of 234 undergoing bilateral salpingo-oophorectomy, 12 (5%) mild to moderate adverse surgical events were recorded. CONCLUSIONS: Bilateral salpingo-oophorectomy is used frequently as an endocrine ablation strategy. Older age was associated with bilateral salpingo-oophorectomy. Perioperative morbidity was acceptable. Evaluation of long-term effects and quality of life associated with endocrine ablation will help guide patient/provider decision-making.

A single-arm clinical trial investigating the effectiveness of a non-hormonal, hyaluronic acid-based vaginal moisturizer in endometrial cancer survivors.

OBJECTIVE: To assess the efficacy of non-hormonal, hyaluronic acid (HLA)-based vaginal gel in improving vulvovaginal estrogen-deprivation symptoms in women with a history of endometrial cancer. METHODS: For this single-arm, prospective, longitudinal trial, we enrolled disease-free women with a history of endometrial cancer who underwent surgery (total hysterectomy) and postoperative radiation. Participants used HLA daily for the first 2 weeks, and then 3×/week until weeks 12-14; dosage was then increased to 5×/week for non-responders. Vulvovaginal symptoms and pH were assessed at 4 time points (baseline [T1]; 4-6 weeks [T2]; 12-14 weeks [T3]; 22-24 weeks [T4]) with clinical evaluation, the Vaginal Assessment Scale (VAS), Vulvar Assessment Scale (VuAS), Female Sexual Function Index (FSFI), and Menopausal Symptom Checklist (MSCL). RESULTS: Of 43 patients, mean age was 59 years (range, 38-78); 54% (23/43) were partnered; and 49% (21/43) were sexually active. VAS, VuAS, MSCL, and SAQ (Sexual Activity Questionnaire) scores significantly improved from baseline to each assessment point (all p < .002). FSFI total mean scores significantly increased from T1 to T2 (p < .05) and from T1 to T4 (p < .03). At T1, 41% (16/39) felt confident about future sexual activity compared to 68% (17/25) at T4 (p = .096). Severely elevated vaginal pH (>6.5) decreased from 30% (13/43) at T1 to 19% (5/26) at T4 (p = .41). CONCLUSION: The HLA-based gel improved vulvovaginal health and sexual function of endometrial cancer survivors in perceived symptoms and clinical exam outcomes. HLA administration 1-2×/week is recommended for women in natural menopause; a 3-5×/week schedule appears more effective for symptom relief in cancer survivors.

Pilot study of rapid MR pancreas screening for patients with BRCA mutation.

PURPOSE: To develop and optimize a rapid magnetic resonance imaging (MRI) screening protocol for pancreatic cancer to be performed in conjunction with breast MRI screening in breast cancer susceptibility gene (BRCA)-positive individuals. METHODS: An IRB-approved prospective study was conducted. The rapid screening pancreatic MR protocol was designed to be less than 10 min to be performed after a standard breast MRI protocol. Protocol consisted of coronal NT T2 SSFSE, axial NT T2 SSFSE and axial NT rFOV FOCUS DWI, and axial T1. Images were acquired with the patient in the same prone position of breast MRI using the built-in body coil. Image quality was qualitatively assessed by two radiologists with 12 and 13 years of MRI experience, respectively. The imaging protocol was modified until an endpoint of five consecutive patients with high-quality diagnostic images were achieved. Signal-to-noise ratio and contrast-to-noise ratio were assessed. RESULTS: The rapid pancreas MR protocol was successfully completed in all patients. Diagnostic image quality was achieved for all patients. Excellent image quality was achieved for low b values; however, image quality at higher b values was more variable. In one patient, a pancreatic neuroendocrine tumor was found and the patient was treated surgically. In four patients, small pancreatic cystic lesions were detected. In one subject, a hepatic mass was identified and confirmed as adenoma by liver MRI. CONCLUSION: Rapid MR protocol for pancreatic cancer screening is feasible and has the potential to play a role in screening BRCA patients undergoing breast MRI. KEY POINT: • Develop and optimize a rapid magnetic resonance imaging (MRI) screening protocol for pancreatic cancer to be performed in conjunction with breast MRI screening in BRCA mutation positive individuals.

Sexual health needs and educational intervention preferences for women with cancer.

PURPOSE: To assess sexual/vaginal health issues and educational intervention preferences in women with a history of breast or gynecologic cancer. METHODS: Patients/survivors completed a cross-sectional survey at their outpatient visits. Main outcome measures were sexual dysfunction prevalence, type of sexual/vaginal issues, awareness of treatments, and preferred intervention modalities. Descriptive frequencies were performed, and results were dichotomized by age, treatment status, and disease site. RESULTS: Of 218 eligible participants, 109 (50%) had a history of gynecologic and 109 (50%) a history of breast cancer. Median age was 49 years (range 21-75); 61% were married/cohabitating. Seventy percent (n = 153) were somewhat-to-very concerned about sexual function/vaginal health, 55% (n = 120) reported vaginal dryness, 39% (n = 84) vaginal pain, and 51% (n = 112) libido loss. Many had heard of vaginal lubricants, moisturizers, and pelvic floor exercises (97, 72, and 57%, respectively). Seventy-four percent (n = 161) had used lubricants, 28% moisturizers (n = 61), and 28% pelvic floor exercises (n = 60). Seventy percent (n = 152) preferred the topic to be raised by the medical team; 48% (n = 105) raised the topic themselves. Most preferred written educational material followed by expert discussion (66%, n = 144/218). Compared to women ≥50 years old (41%, n = 43/105), younger women (54%, n = 61/113) preferred to discuss their concerns face-to-face (p = 0.054). Older women were less interested in online interventions (52%, p < 0.001), despite 94% having computer access. CONCLUSION: Female cancer patients/survivors have unmet sexual/vaginal health needs. Preferences for receiving sexual health information vary by age. Improved physician-patient communication, awareness, and educational resources using proven sexual health promotion strategies can help women cope with treatment side effects.

Validation of Clinical Tools for Vaginal and Vulvar Symptom Assessment in Cancer Patients and Survivors.

INTRODUCTION: Health care professionals can play a pivotal role in promoting vulvovaginal health through assessment and appropriate intervention. AIM: To develop and validate brief clinical measurements to facilitate the identification of vulvovaginal symptoms in patients with and survivors of cancer. METHODS: One hundred seventy-five women survivors of cancer attending a Female Sexual Medicine and Women's Health Program from September 26, 2012 through October 31, 2014 completed the Vaginal Assessment Scale (VAS) and the Vulvar Assessment Scale (VuAS)-a modified version of the VAS that targets vulvar symptoms. Pelvic examination results were recorded using a clinical examination checklist. MAIN OUTCOME MEASURES: Internal consistency of the two scales was assessed using Cronbach α, and the correlation between scales and other outcomes was reported. RESULTS: The internal consistency measurements of the VAS and VuAS at the first visit were 0.70 and 0.68, which decreased to 0.53 and 0.66 at the last visit. The VAS composite and VuAS composite scores were moderately correlated with each other (0.42 and 0.45 at first and last visits, respectively). A strong correlation was observed between VAS pain with intercourse and Female Sexual Function Index (FSFI) pain with intercourse (-0.63 and -0.71 at the first and last visits, respectively). Worse pain with examination, worse functioning on the FSFI pain, lubrication, and total scores, and worse vulvar irritation were correlated with more severe symptoms on the VAS and VuAS. CONCLUSION: The VAS and VuAS are simple tools that can be used by clinicians to assess health concerns in women diagnosed with and treated for cancer. Validation is needed across diverse settings and groups of women.

Baseline characteristics and concerns of female cancer patients/survivors seeking treatment at a Female Sexual Medicine Program.

PURPOSE: The purpose of this study is to characterize patients seeking treatment at a Female Sexual Medicine and Women's Health Program and examine their sexual/vaginal health issues. METHODS: Data from clinical assessment forms were extracted from 509 women referred to the Female Sexual Medicine and Women's Health Program during/after cancer treatment. The form consists of a Vaginal Assessment Scale (VAS), vaginal health items, patient-reported outcomes (PROs) (Sexual Activity Questionnaire [SAQ], Sexual Self-Schema Scale [SSS], Female Sexual Function Index [FSFI]), and exploratory items. RESULTS: Of 509 patients, 493 (97 %) completed PROs; 253 (50 %) received a pelvic examination. The majority had a history of breast (n = 260, 51 %), gynecologic (n = 184, 36 %), or colorectal/anal (n = 35, 7 %) cancer. Mean age was 51.2 years; 313 (62 %) were married/partnered. Approximately two thirds had elevated vaginal pH scores (5-6.5 [35 %] or 6.5+ [33 %]) and minimal (62 %) or no (5 %) vaginal moisture. Eighty-seven patients (44 %) experienced pain during their exam (23 % mild, 11 % moderate, 1.5 % severe, and 8.5 % not indicated). Fifty-three percent engaged in sexual activity with a partner; only 43 % felt confident about future sexual activity. Ninety-three percent were somewhat to very concerned/worried about sexual function/vaginal health. Approximately half had moderate/severe dryness (n = 133, 51 %) and dyspareunia (n = 120, 46 %). The mean SSS score was 60.7, indicating a slightly positive sexual self-view. However, 93.5 % (n = 429) had an FSFI score <26.55, suggesting sexual dysfunction. CONCLUSIONS: At initial consult, women reported vaginal dryness, pain, and sexual dysfunction. For many women, pelvic exams showed elevated vaginal pH, lack of moisture, and discomfort with the exam itself. Future analyses will examine changes over time.

Risk-Reducing Bilateral Salpingo-Oophorectomy for Ovarian Cancer: A Review and Clinical Guide for Hereditary Predisposition Genes.

Pathogenic germline variants underlie up to 20% of ovarian cancer (OC) and are associated with varying degrees of risk for OC. For mutations in high-penetrance genes such as BRCA1/2, the role of risk-reducing bilateral salpingo-oophorectomy (RRSO) in cancer prevention is well-established and improves mortality. However, in moderate-penetrance genes where the degree of risk for OC is less precisely defined, the role of RRSO is more controversial. Although national guidelines have evolved to incorporate gene-specific recommendations, studies demonstrate significant variations in practice. Given this, our multidisciplinary group has reviewed the available literature on risk estimates for genes associated with OC, incorporated levels of evidence, and set thresholds for consideration of RRSO. We found that the benefit of RRSO is well-established for pathogenic variants in BRCA1/2 as well as BRIP1 and RAD51C/D where the risk of OC is elevated beyond our threshold for RRSO. In PALB2, RRSO is particularly controversial as newer studies consistently demonstrate an increased risk of OC that is dependent on family history, making uniform recommendations challenging. Additionally, new guidelines for Lynch syndrome provide gene-specific risks, questioning the role of RRSO, and even hysterectomy, for MSH6 and PMS2 mutation carriers. Given these uncertainties, shared decision making should be used around RRSO with discussion of individual risk factors, family history, and adverse effects of surgery and premature menopause. Herein, we provide a clinical guide and counseling points.

Gynecologic Survivorship Tool: Development, Implementation, and Symptom Outcomes.

PURPOSE: To describe the development and implementation of a new digital health clinical tool (Gynecologic Survivorship Tool [GST]) for symptom management of women surgically treated for gynecologic cancer; to assess its feasibility; and to conduct a retrospective review of the data. MATERIALS AND METHODS: The GST was developed on the basis of a comprehensive review of the literature, multidisciplinary expert opinion, and feedback from women with a history of gynecologic cancer. It is composed of 17 questions addressing six main categories-gynecologic health (abnormal bleeding/pain), lymphedema, vaginal/vulvar dryness, sexual health, menopause (hot flushes/sleep difficulties), and bowel/urinary issues. An electronic version using the Memorial Sloan Kettering Cancer Center Engage platform was piloted in two clinics for patients with endometrial or cervical cancer. Health information was generated into clinical summaries and identified concerns for actionable response. Associations of symptom and survey time point were assessed by longitudinal models using generalized estimating equations. RESULTS: From January 1, 2019, to February 29, 2020, 3,357 GST assessments were assigned to 1,405 patients, with a 71% completion rate (90% within 5 minutes). Sixty-eight percent were performed at home via a patient portal, 32% at follow-ups using a clinic iPad. The most common symptoms were bowel problems, swelling/fluid, pain during examination, vaginal or vulvar dryness, and vaginal bleeding. Implementation challenges included improving patient compliance and ensuring that reports were reviewed by all clinical teams. We developed screening e-mails detailing patients whose assessments were due, planned training sessions for multidisciplinary teams, and incorporated feedback on methods for reviewing symptoms reports. CONCLUSION: The GST demonstrated feasibility, a high completion rate, and minimal time commitment. It was an effective electronic reporting mechanism for patients, enabling the medical team to develop specific strategies for alleviating bothersome symptoms during follow-up.

Simple strategies for vaginal health promotion in cancer survivors.

INTRODUCTION: With the population of cancer survivors nearing 12 million, an ever-increasing number of women will face vaginal health issues related to their disease and/or treatment. Abrupt menopause triggered by cancer treatment, for example, can cause intense and prolonged estrogen deprivation symptoms, including vaginal dryness and discomfort. Simple strategies to promote vaginal health are available. AIMS: To provide a comprehensive overview of vaginal health issues caused by estrogen deprivation in female cancer patients/survivors and provide recommendations to identify, treat, and promote vaginal health. METHODS: We describe a treatment algorithm, based on scientific literature and supported by clinical experience, found to be effective in treating these patients at two major cancer centers. We also provide examples of handouts for patient education on vaginal health promotion. MAIN OUTCOME MEASURES: Evidence-based medicine and psychosocial literature, in addition to clinical experience at two major cancer centers. RESULTS: Simple, non-hormonal interventions for sexual dysfunction are often overlooked. Several studies show that education on vaginal lubricants, moisturizers, and dilator use (as needed) can decrease the morbidity of vaginal atrophy. These studies also provide support for our clinical treatment recommendations. Our goal in this article is to increase awareness of these strategies and to provide assistance to general gynecologists and oncologists caring for cancer patients and survivors. CONCLUSIONS: Dedicating a small amount of time to educate female cancer survivors about methods to promote vaginal health can result in the reduction or elimination of vaginal discomfort. Non-hormonal vaginal health strategies often appear sufficient to remedy these issues. However, large randomized trials are needed, varying the format and components of the treatment program and exploring efficacy in various groups of female cancer survivors.

Sexual Function in Women with Colorectal/Anal Cancer.

BACKGROUND: Treatments for colorectal and anal cancers can have a detrimental impact on sexual function. Type of treatment, which may include surgery, radiation, and/or chemotherapy, varies by disease site and severity. Treatment and long-term side effects can impact sexual function and intimacy for patients and their partners. AIM: To review the literature regarding treatment for colorectal/anal cancer and its impact on female sexual function, and to provide an assessment of medical outcomes and patient-reported outcomes (PROs) of women with a history of colon, rectal, or anal cancer seeking sexual health treatment. METHODS: We performed a PubMed search to identify peer-reviewed, English-language articles published between 2008 to 2018, using the following search terms: "colorectal cancer," or "rectal cancer," or "anal cancer" and "sexual function," or "sexual dysfunction." We also assessed the medical outcomes and PROs from our recent cross-sectional cohort study of 99 women with a history of colon, rectal, or anal cancer seeking sexual health treatment. MAIN OUTCOME MEASURES: Sexual function, quality of life, and PROs after colorectal/anal cancer. RESULTS: A total of 23 studies were identified. Study designs included 15 cross-sectional survey studies, 5 longitudinal studies, 2 psychoeducational interventions, and 1 pilot study. 10 studies included only women, and 13 included both men and women. The literature and our cohort confirmed that women with colorectal/anal cancer experience changes in sexual function after diagnosis and throughout the continuum of care; however, the scarcity of data in this area indicates a need for additional intervention trials and longitudinal studies. CONCLUSIONS: Research studies with large sample sizes and long study durations are needed to help us better understand the needs of female survivors of colorectal/anal cancer. Women with colorectal/anal cancer need simple strategies and resources to address concerns of sexual function after cancer treatment. Such interventions have been shown to enhance survivorship and quality of life. Canty J, Stabile C, Milli L, et al. Sexual Function in Women with Colorectal/Anal Cancer. Sex Med Rev 2019;7:202-222.

Reducing False-Positive Pregnancy Test Results in Patients With Cancer.

OBJECTIVE: To assess whether the use of a laboratory test specific for intact human chorionic gonadotropin (hCG) would reduce the number of false-positive pregnancy test results. METHODS: From October 21, 2014, to January 20, 2015, and April 1, 2015, to June 2, 2015, all serum samples sent for pregnancy screening at a large cancer center with a value of 5 milli-international units/mL or greater total ß-hCG were frozen and stored and then retested using intact hCG reagent. We compared the accuracy of total ß-hCG and intact hCG results for the diagnosis of clinically confirmed pregnancy. A negative test was defined as 14 milli-international units/mL or less, our current institutional cutoff. We also assessed a cutoff of less than 5 milli-international units/mL, a historical cutoff to rule out pregnancy. RESULTS: We performed intact hCG testing on 64 patient samples, of which 34 had originally resulted positive when tested for total ß-hCG. These included 21 cases of clinically confirmed pregnancy and 13 false-positive cases. No women were pregnant when their intact hCG concentration was 14 milli-international units/mL or less, and all pregnancies were detected at and above this concentration. Intact hCG reduced the number of false-positive pregnancy test results from 13 to 1, a 92% reduction (95% CI 64-99%), corresponding to a reduction in the false-positive rate from 38% (95% CI 22-56%) to 3% (95% CI 1-15%). CONCLUSION: The use of intact hCG reagent in patients with cancer reduces the rate of false-positive pregnancy test results without increasing the rate of false-negative test results.

Vaginal and sexual health treatment strategies within a female sexual medicine program for cancer patients and survivors.

PURPOSE: We sought to evaluate patient adherence and response to simple vaginal and sexual health treatment strategies in female cancer patients receiving treatment at a female sexual medicine and health program and identify improvements of physical symptoms, per patient and clinical evaluation. METHODS: Evaluability criteria included gynecologic exam at initial visit, at least one follow-up with gynecologic exam within 8 months of initial visit, and all consecutive follow-ups <6 months apart. Demographics, medical information, and clinical assessments from 175 evaluable patients with at least one follow-up from 09/12 to 10/14 were analyzed. The majority of patients were being treated for or had a history of breast (n = 90, 53 %), gynecologic (n = 54, 32 %), or colorectal/anal (n = 15, 9 %) cancers. An assessment form included a clinician evaluation, Vaginal Assessment Scale (VAS), Vulvar Assessment Scale (VuAS), and patient-reported outcomes. Compliance with treatment recommendations were summarized, and changes over time were compared for clinical outcomes. RESULTS: Mean number of visits was 3.43. Mean age was 55.4 years; 92 % (n = 155/169) were in menopause. Treatment strategies included rationale and instruction for use of vaginal moisturizers, lubricants, pelvic floor exercises, and dilator therapy, in addition to psychosexual education regarding sexual changes (response, anatomy, and function) associated with cancer treatment and support. At last assessment, 89 % had complied with the clinical recommendation (moisturize 2-5+ times/week). Vaginal pH scores >6.5 declined over time (p = 0.03). VAS scores improved by last assessment (p < 0.001), as did VuAS scores (p = 0.001). Sexual function scores significantly improved (p < 0.001), confidence about future sexual activity increased (p = 0.004), and sexual/vaginal health concerns decreased (p = 0.00003). CONCLUSION: Significant changes were observed in women using treatment strategies, with improvement in vulvovaginal symptoms, a decrease in elevated vaginal pH and pain with exams, enhanced sexual function, and increased intimacy confidence. IMPLICATIONS FOR CANCER SURVIVORS: These findings have high clinical relevance for symptom management with improvement of sexual function using simple strategies and clinical tools in the oncology setting.

Effect of mammography on breast cancer risk in women with mutations in BRCA1 or BRCA2.

Women who carry mutations in either the BRCA1 or BRCA2 genes are at risk for early-onset breast cancer and are recommended to begin screening mammography at age 25 to 30 years. Results of in vitro and animal studies suggest that BRCA1/BRCA2 mutation carriers are hypersensitive to ionizing radiation and possibly to radiation-induced breast cancer. This study was undertaken to investigate the association of low-dose radiation exposure from mammograms with breast cancer status in BRCA mutation carriers. One hundred sixty-two female mutation carriers provided information at time of genetic testing about exposure to mammograms before enrollment. Using unconditional logistic regression, breast cancer status was not associated with number of mammograms received before diagnosis (affected women) or ascertainment [unaffected women; adjusted odds ratio (OR), 0.94; P = not significant]. A larger group of 213 women provided information about lifetime number of mammograms. There was no association between mammogram exposure and risk in the group as a whole (adjusted OR, 1.04; P = not significant), although there was a modest association in BRCA1 carriers (adjusted OR, 1.08; P = 0.03). These findings indicate that screening mammography is unlikely to be associated with a large increase in breast cancer risk in this population.

Uterine Cancer After Risk-Reducing Salpingo-oophorectomy Without Hysterectomy in Women With BRCA Mutations.

IMPORTANCE: The link between BRCA mutations and uterine cancer is unclear. Therefore, although risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations (BRCA+ women), the role of concomitant hysterectomy is controversial. OBJECTIVE: To determine the risk for uterine cancer and distribution of specific histologic subtypes in BRCA+ women after RRSO without hysterectomy. DESIGN, SETTING, AND PARTICIPANTS: This multicenter prospective cohort study included 1083 women with a deleterious BRCA1 or BRCA2 mutation identified from January 1, 1995, to December 31, 2011, at 9 academic medical centers in the United States and the United Kingdom who underwent RRSO without a prior or concomitant hysterectomy. Of these, 627 participants were BRCA1+; 453, BRCA2+; and 3, both. Participants were prospectively followed up for a median 5.1 (interquartile range [IQR], 3.0-8.4) years after ascertainment, BRCA testing, or RRSO (whichever occurred last). Follow up data available through October 14, 2014, were included in the analyses. Censoring occurred at uterine cancer diagnosis, hysterectomy, last follow-up, or death. New cancers were categorized by histologic subtype, and available tumors were analyzed for loss of the wild-type BRCA gene and/or protein expression. MAIN OUTCOMES AND MEASURES: Incidence of uterine corpus cancer in BRCA+ women who underwent RRSO without hysterectomy compared with rates expected from the Surveillance, Epidemiology, and End Results database. RESULTS: Among the 1083 women women who underwent RRSO without hysterectomy at a median age 45.6 (IQR: 40.9 - 52.5), 8 incident uterine cancers were observed (4.3 expected; observed to expected [O:E] ratio, 1.9; 95% CI, 0.8-3.7; P = .09). No increased risk for endometrioid endometrial carcinoma or sarcoma was found after stratifying by subtype. Five serous and/or serous-like (serous/serous-like) endometrial carcinomas were observed (4 BRCA1+ and 1 BRCA2+) 7.2 to 12.9 years after RRSO (BRCA1: 0.18 expected [O:E ratio, 22.2; 95% CI, 6.1-56.9; P < .001]; BRCA2: 0.16 expected [O:E ratio, 6.4; 95% CI, 0.2-35.5; P = .15]). Tumor analyses confirmed loss of the wild-type BRCA1 gene and/or protein expression in all 3 available serous/serous-like BRCA1+ tumors. CONCLUSIONS AND RELEVANCE: Although the overall risk for uterine cancer after RRSO was not increased, the risk for serous/serous-like endometrial carcinoma was increased in BRCA1+ women. This risk should be considered when discussing the advantages and risks of hysterectomy at the time of RRSO in BRCA1+ women.

Hereditary ovarian cancer in Ashkenazi Jews.

Ovarian cancer is the fourth leading cause of cancer deaths among American women. While women in both the Ashkenazi and non-Ashkenazi populations have an estimated 1.7% lifetime risk of acquiring malignancy, the proportion of hereditary ovarian cancer is much higher in the Ashkenazim. Most of this increased proportion of hereditary ovarian cancer risk is accounted for by inherited mutations in the BRCA1 and BRCA2 genes. In the Ashkenazi Jewish population, 29 to 41% of ovarian cancer is believed to be secondary to inheriting one of three founder mutations in BRCA 1 and BRCA 2, while only 10% of ovarian cancer is attributed to mutations of these genes in non-Ashkenazim. In the US population in general, it is estimated that between 1 out of 345 and 1 out of 1000 individuals carries a BRCA mutation, compared with approximately 1 in 40 individuals of Ashkenazi Jewish descent. The ovarian cancer risk up to age 70 associated with BRCA mutation carriers has been reported to be as high as 66% for BRCA1 and 27% for BRCA2 mutation carriers. Ovarian cancer in Ashkenazi kindreds has served as a model for the study of the histopathology of inherited ovarian cancers as well as for the study of risk reduction and screening among all women at inherited risk of ovarian cancer.

Risk of ovarian cancer in BRCA1 and BRCA2 mutation-negative hereditary breast cancer families.

Women from site-specific hereditary breast cancer families who carry a BRCA1 or BRCA2 mutation are at increased risk for ovarian cancer. It is less clear, however, whether individuals from hereditary breast cancer families who do not carry such a mutation are also at increased ovarian cancer risk. To determine whether women from BRCA mutation-negative hereditary breast cancer families are at increased risk for ovarian cancer, 199 probands from BRCA mutation-negative, site-specific breast cancer kindreds who consented to prospective follow-up at the time of genetic testing were identified. The incidence of new breast and ovarian cancers in probands and their families since receipt of their genetic test results was determined by questionnaire. The expected number of cancers and standardized incidence ratios (SIRs) were determined from age-specific cancer incidence rates from the Surveillance, Epidemiology, and End Results (SEER) program by using the method of Byar. All statistical tests were two-sided. During 2534 women-years of follow-up in 165 kindreds, 19 new cases of breast cancer were diagnosed, whereas only 6.07 were expected (SIR = 3.13, 95% confidence interval [CI] = 1.88 to 4.89; P < .001), and one case of ovarian cancer was diagnosed, whereas only 0.66 was expected (SIR = 1.52, 95% CI = 0.02 to 8.46; P = .48). These results suggest that women from BRCA mutation-negative, site-specific breast cancer families are not at increased risk for ovarian cancer.

Ovarian carcinoma screening in women at intermediate risk: impact on quality of life and need for invasive follow-up.

BACKGROUND: Women with family histories suggestive of an increased risk of ovarian carcinoma who have not had a deleterious BRCA1 or BRCA2 mutation identified are commonly suggested to consider ovarian carcinoma screening with transvaginal ultrasound and/or assessment of CA 125 levels. Limited information is available regarding the impact of this approach on either quality of life (QOL) or need for invasive follow-up in this group of women. METHODS: From November 1999 to October 2002, 184 women at intermediate risk of ovarian carcinoma were enrolled in a prospective study. Participants were screened with twice yearly transvaginal ultrasound and CA 125 assessments. Impact on QOL was measured using the Mental Component Summary (MCS) score of the Medical Outcomes Studies Short Form-36. Need for invasive follow-up was determined by questionnaire and medical record review. RESULTS: In the current study, 135 participants underwent > or = 1 follow-up assessment. During a mean of 19.8 months of follow-up, 12.9% of ultrasounds and 3.8% of CA 125 assessments were abnormal. The authors reported that 38.5% of participants had > or = 1 abnormal ovarian screen that required a short interval follow-up. Because of either abnormal bleeding or ultrasound abnormalities, 24% of participants underwent > or = 1 endometrial sampling. Controlling for a history of breast carcinoma and menopausal status, abnormal ovarian screening results were associated with a decrease in MCS score (P = 0.034), whereas the need for endometrial sampling was not (P = 0.87). CONCLUSIONS: Ovarian carcinoma screening in women at intermediate risk was associated with a substantial rate of abnormal screen results, endometrial sampling, and in women with abnormal ovarian screening findings, a decrease in MCS scores. These findings may have important implications for women considering ovarian carcinoma screening and for the design of future ovarian carcinoma screening trials.