Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of the Cancer Care Ontario Guideline.

PURPOSE: To update the American Society of Clinical Oncology endorsement of the Cancer Care Ontario recommendations on the Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision Making for Early-Stage, Operable Breast Cancer. METHODS: Two phase III trials-the Trial Assigning Individualized Options for Treatment (TAILORx) in women with hormone receptor-positive, node-negative tumors and the Microarray in Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy (MINDACT) trial-provided the evidence for this update. UPDATED RECOMMENDATIONS: Shared decision making between clinicians and patients is appropriate for adjuvant systemic therapy for breast cancer. For patients older than age 50 years and whose tumors have Oncotype DX recurrence scores less than 26, and for patients age 50 years or younger whose tumors have Oncotype DX recurrence scores less than 16, there is little to no benefit from chemotherapy. Clinicians may offer endocrine therapy alone for these patients. For patients age 50 years or younger with recurrence scores of 16 to 25, clinicians may offer chemoendocrine therapy. Patients with recurrence scores greater than 30 should be considered candidates for chemoendocrine therapy. Based on informal consensus, the Panel recommends that oncologists may offer chemoendocrine therapy to patients with Oncotype DX scores of 26 to 30.The MammaPrint assay could be used to guide decisions on withholding adjuvant systemic chemotherapy in patients with hormone receptor-positive lymph node-negative breast cancer and in select patients with lymph node-positive cancers. In both patients with node-positive and node-negative disease, evidence of clinical utility of the MammaPrint assay was only apparent in those determined to be at high clinical risk; the Panel thus did not recommend use of MammaPrint assay in patients determined to be at low clinical risk. Remaining recommendations from the 2016 ASCO guideline endorsement are unchanged.Additional information is available at www.asco.org/breast-cancer-guidelines.

Efficacy of a web-based women's health survivorship care plan for young breast cancer survivors: a randomized controlled trial.

PURPOSE: Breast cancer survivorship care plans (SCP) have limited content addressing women's health issues. This trial tested if young breast cancer survivors who receive a web-based, women's health SCP were more likely to improve on at least one of the four targeted issues (hot flashes, fertility-related concerns, contraception, and vaginal symptoms) compared to attention controls. METHODS: A randomized controlled trial recruited female survivors ages 18-45 at diagnosis, 18-50 at enrollment, completed primary cancer treatment, and had a significant women's health issue: moderate or higher fertility-related concerns; ≥ 4 hot flashes/day with ≥ 1 of moderate severity; ≥ 1 moderate vaginal atrophy symptoms; or not contracepting/using less effective methods. Survivors underwent stratified, block randomization with equal allocation to intervention and control groups. The intervention group accessed the online SCP; controls accessed curated resource lists. In intention-to-treat analysis, the primary outcome of improvement in at least one issue by 24 weeks was compared by group. RESULTS: 182 participants (86 intervention, 96 control), mean age 40.0 ± 5.9 and 4.4 ± 3.2 years since diagnosis, were randomized. 61 intervention group participants (70.9%) improved, compared to 55 controls (57.3%) (OR 1.82, 95% CI 0.99-3.4, p = 0.057). The following issue-specific improvements were observed in the intervention versus control arms: fertility-related concerns (27.9% vs. 14.6%, OR 2.3, 95% CI 1.1-4.8); hot flashes (58.5% vs. 55.8%, OR 1.1, 95% CI 0.57-2.2); vaginal symptoms (42.5% vs. 40.7%, OR 1.1, 95% CI 0.6-2.0); contraception (50% vs. 42.6%, OR 1.4, 95% CI 0.74-2.5). CONCLUSIONS: In young breast cancer survivors, a novel, web-based SCP did not result in more change in the primary outcome of improvement in at least one of the four targeted women's health issues, than the attention control condition. The intervention was associated with improved infertility concerns, supporting efficacy of disseminating accessible, evidence-based women's health information to this population.

Design of a randomized controlled trial on the efficacy of a reproductive health survivorship care plan in young breast cancer survivors.

BACKGROUND: Young breast cancer survivors (YBCS) have unmet needs for managing hot flashes, fertility-related concerns, sexual health, and contraception. PURPOSE: Describe the design and participant characteristics of a randomized controlled trial testing the efficacy of the survivorship care plan on reproductive health (SCP-R) intervention on improving hot flashes, fertility-related concerns, sexual health, and contraception in YBCS. METHODS: SCP-R is a web-based intervention with text message support encompassing evidence- based practices on four reproductive health issues. YBCS with ≥1 reproductive health issue are randomized to intervention (full SCP-R access) or attention control (access to list of online resources) arms with 24-week follow-up. The primary outcome will be improvement of at least one reproductive health issue measured by validated self-report instruments. Each YBCS nominated one healthcare provider (HCP), who can access the same materials as their patient. HCP outcomes are preparedness and confidence in discussing each issue. RESULTS: Among 318 YBCS screened, 57.2% underwent randomization. Mean age was 40.0 (SD 5.9), and mean age at cancer diagnosis was 35.6 (SD 5.4). Significant hot flashes, fertility-related concerns, vaginal symptoms, and inadequate contraception were reported by 50.5%, 50%, 46.7%, 62.1% of YBCS, respectively; 70.9% had multiple issues. Among 165 nominated HCPs, 32.7% enrolled. The majority of HCPs reported preparedness (68.5-90.7%) and confidence (50.0-74.1%) in discussing reproductive health issues with YBCS. HCPs were least likely to report preparedness or confidence in discussing fertility-related concerns. CONCLUSION: Conducting a trial for improving YBCS reproductive health online is feasible, providing a mechanism to disseminate evidence-based management.

Patient-Reported Outcomes in Cancer Clinical Trials: Measuring Symptomatic Adverse Events With the National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

Systematic capture of the patient perspective can inform the development of new cancer therapies. Patient-reported outcomes (PROs) are commonly included in cancer clinical trials; however, there is heterogeneity in the constructs, measures, and analytic approaches that have been used making these endpoints challenging to interpret. There is renewed effort to identify rigorous methods to obtain high-quality and informative PRO data from cancer clinical trials. In this setting, PROs are used to address specific research objectives, and an important objective that spans the product development life cycle is the assessment of safety and tolerability. The U.S. Food and Drug Administration's (FDA) Office of Hematology and Oncology Products (OHOP) has identified symptomatic adverse events (AEs) as a central PRO concept, and a systematic assessment of patient-reported symptomatic AEs can provide data to complement clinician reporting. The National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is being evaluated by multiple stakeholders, including the FDA, and is considered a promising tool to provide a standard yet flexible method to assess symptomatic AEs from the patient perspective. In this article, we briefly review the FDA OHOP's perspective on PROs in cancer trials submitted to the FDA and focus on the assessment of symptomatic AEs using PRO-CTCAE. We conclude by discussing further work that must be done to broaden the use of PRO-CTCAE as a method to provide patient-centered data that can complement existing safety and tolerability assessments across cancer clinical trials.

Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision Making for Early-Stage, Operable Breast Cancer: American Society of Clinical Oncology Endorsement of Cancer Care Ontario Guideline Recommendations.

PURPOSE: An American Society of Clinical Oncology (ASCO) panel considered the Cancer Care Ontario (CCO) recommendations on the role of patient and disease factors in selecting adjuvant therapy for women with early-stage breast cancer for endorsement. METHODS: ASCO staff reviewed the CCO guideline for methodologic rigor, and an ASCO panel of content experts reviewed the content of the recommendations. CCO RECOMMENDATIONS: For making decisions regarding adjuvant therapy, nodal status, tumor size, estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) status, tumor grade, and lymphovascular invasion are relevant; Oncotype DX score and Adjuvant! Online may be used as risk stratification tools; and age, menopausal status, and medical comorbidities should be considered. Chemotherapy should be considered for patients with positive lymph nodes, ER-negative disease, HER2-positive disease, Adjuvant! Online mortality greater than 10%, grade 3 lymph node-negative tumors (T > 5 mm), triple-negative (ER-negative, PgR-negative, HER2-negative) tumors, lymphovascular invasion positivity, or estimated distant relapse risk of greater than 15% at 10 years based on Oncotype DX recurrence score (RS). Chemotherapy may not be beneficial or required for small node-negative tumors (T < 5 mm) without high-risk features or for patients with HER2-negative, strongly ER-positive, and PgR-positive cancer with micrometastatic nodal disease, T less than 5 mm, or Oncotype DX RS with an estimated distant relapse risk of less than 15% at 10 years. ASCO PANEL CONCLUSION: The ASCO panel endorses the recommendations with minor suggested revisions and highlights three areas that warrant further consideration: tumor histology and adjuvant therapy recommendations, risk stratification tools and proposed Oncotype DX RS thresholds to guide decisions about chemotherapy, and patient factors in decision making.

Outcomes and endpoints in cancer trials: bridging the divide.

Cancer is not one disease. Outcomes and endpoints in trials should incorporate the therapeutic modality and cancer type because these factors affect clinician and patient expectations. In this Review, we discuss how to: define the importance of endpoints; make endpoints understandable to patients; improve the use of patient-reported outcomes; advance endpoints to parallel changes in trial design and therapeutic interventions; and integrate these improvements into trials and practice. Endpoints need to reflect benefit to patients, and show that changes in tumour size either in absolute terms (response and progression) or relative to control (progression) are clinically relevant. Improvements in trial design should be accompanied by improvements in available endpoints. Stakeholders need to come together to determine the best approach for research that ensures accountability and optimises the use of available resources.

Management of sexual dysfunction in breast cancer survivors: a systematic review.

Female sexual dysfunction occurs frequently in midlife breast cancer survivors (BCS) and encompasses problems with sexual desire, interest, arousal, orgasm and genitopelvic pain. Although common, sexual problems are under-diagnosed and under-treated in BCS. The objective of this review was to assess primary studies that intervene on sexual dysfunction in BCS. In February 2015, PubMed, SCOPUS, CINAHL, COCHRANE and Web of Science databases were systematically searched for randomized controlled clinical trials (RCTs) of vaginal (lubricants, moisturizers, estrogens, dehydroepiandrosterone [DHEA], testosterone, vibrators, dilators), systemic (androgens, anti-depressants, flibanserin, ospemifene), physical therapy (physical activity, pelvic floor training), counseling and educational interventions on sexual function in BCS. Observational studies of vaginal interventions were also included due to the paucity of RCTs. The search yielded 1414 studies, 34 of which met inclusion criteria. Both interventions and outcomes, measured by 31 different sexual function scales, were heterogeneous, and therefore data were not pooled. The review found that regular and prolonged use of vaginal moisturizers was effective in improving vaginal dryness, dyspareunia, and sexual satisfaction. Educational and counseling interventions targeting sexual dysfunction showed consistent improvement in various aspects of sexual health. No consistent improvements in sexual health were observed with physical activity, transdermal testosterone or hot flash interventions. There was a lack of BCS-specific data on vaginal lubricants, vibrators, dilators, pelvic floor therapy, flibanserin or ospemifene. Overall, the quality of evidence for these studies was moderate to very low. Because each of the interventions with BCS data had limited efficacy, clinical trials to test novel interventions are needed to provide evidence-based clinical recommendations and improve sexual function in BCS.