Attempted replication of pharmacogenetic association of variants in PPP1R14C and CCDC148 with aromatase inhibitor-induced musculoskeletal symptoms.

Third-generation aromatase inhibitors (AI) are the standard treatment for patients with hormone receptor positive (HR+) breast cancer. While effective, AI can lead to severe adverse events, including AI-induced musculoskeletal syndrome (AIMSS). Genetic predictors of AIMSS have the potential to personalize AI treatment and improve outcomes. We attempted to replicate results from a previous genome-wide association study that found a lower risk of AIMSS in patients carrying PPP1R14C rs912571 and a higher risk in patients carrying CCDC148 rs79048288. AIMSS data were collected prospectively from patients with HR+ breast cancer prior to starting and after 3 and 6 months of adjuvant AI via the Patient-Reported Outcome Measurement Information System and Functional Assessment of Cancer Therapy-Endocrine Symptom. Germline genotypes for PPP1R14C rs912571 and CCDC148 rs79048288 were tested for a similar association with AIMSS as previously reported via $2 tests. Of the 143 patients with AIMSS and genetics data were included in the analysis. There was no association identified between PPP1R14C rs912571 and AIMSS risk ( P  > 0.05). Patients carrying CCDC148 rs79048288 variant alleles had lower AIMSS incidence in a secondary analysis ( P  = 0.04); however, this was in the opposite direction of the previous finding. The study did not replicate previously reported associations with AIMSS risk for genetic variants in PPP1R14C and CCDC148 and AIMSS risk. Further research is needed to discover and validate genetic predictors of AIMSS that can be used to personalize treatment in patients with HR+ breast cancer.

Factors associated with worsening sexual function during adjuvant endocrine therapy in a prospective clinic-based cohort of women with early-stage breast cancer.

PURPOSE: Sexual function problems are common but under-reported among women receiving adjuvant endocrine therapy for breast cancer. Worsening scores on patient-reported outcomes (PROs) may identify those at risk for sexual function problems during treatment. We performed a secondary analysis of prospectively collected PROs in women receiving adjuvant endocrine therapy to identify factors associated with worsening sexual function. METHODS: Women with stage 0-III breast cancer initiating adjuvant endocrine therapy participating in a prospective cohort completed PROs at baseline, 3, 6, 12, 24, 36, 48, and 60 months. Sexual function was evaluated by the MOS-SP measure. Other measures included PROMIS pain interference, fatigue, depression, anxiety, physical function, and sleep disturbance and the Endocrine Symptom Subscale of the FACT-ES. We evaluated associations between score worsening of at least the minimal important difference (MID) in PROMIS T-scores (4 points) and FACT-ES scores (5 points) with score worsening of at least the MID in MOS-SP scores (8 points) using logistic regression. RESULTS: Among 300 participants, 45.7% experienced ≥ 8-point worsening of MOS-SP score at any time point compared to baseline. Worsening endocrine symptoms (OR 1.34, 95% CI 1.22-1.49, p < 0.001), worsening physical function (OR 1.09, 95% CI 1.00-1.18, p = 0.06), and prior mastectomy (OR 1.45, 95% CI 0.94-2.23, p = 0.09) were associated with MOS-SP score worsening by at least the MID. CONCLUSION: Worsening endocrine symptoms and physical function identified on PROs are associated with worsening sexual function during adjuvant endocrine therapy. Routine assessment of these domains with PROs may identify women at risk for sexual function problems. TRIAL REGISTRATION NUMBER: NCT01937052; Date of Registration: 09/09/2013.

Breast Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. These NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of ductal carcinoma in situ and the workup and locoregional management of early stage invasive breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.

A PRO-cision medicine intervention to personalize cancer care using patient-reported outcomes: intervention development and feasibility-testing.

PURPOSE: PRO-cision medicine refers to personalizing care using patient-reported outcomes (PROs). We developed and feasibility-tested a PRO-cision Medicine remote PRO monitoring intervention designed to identify symptoms and reduce the frequency of routine in-person visits. METHODS: We conducted focus groups and one-on-one interviews with metastatic breast (n = 15) and prostate (n = 15) cancer patients and clinicians (n = 10) to elicit their perspectives on a PRO-cision Medicine intervention's design, value, and concerns. We then feasibility-tested the intervention in 24 patients with metastatic breast cancer over 6-months. We obtained feedback via end-of-study surveys (patients) and interviews (clinicians). RESULTS: Focus group and interview participants reported that remote PRO symptom reporting could alert clinicians to issues and avoid unneeded/unwanted visits. However, some patients did not perceive avoiding visits as beneficial. Clinicians were concerned about workflow. In the feasibility-test, 24/236 screened patients (10%) enrolled. Many patients were already being seen less frequently than monthly (n = 97) or clinicians did not feel comfortable seeing them less frequently than monthly (n = 31). Over the 6-month study, there were 75 total alerts from 392 PRO symptom assessments (average 0.19 alert/assessment). Patients had an average of 4 in-person visits (vs. expected 6.5 without the intervention). Patients (n = 19/24) reported high support on the end-of-study survey, with more than 80% agreeing with positive statements about the intervention. Clinician end-of-study interviews (n = 11/14) suggested that PRO symptom monitoring be added to clinic visits, rather than replacing them, and noted the increasing role of telemedicine. CONCLUSIONS: Future research should explore combining remote PRO symptom monitoring with telemedicine and in-person visits.

NCCN Guidelines® Insights: Breast Cancer, Version 4.2021.

The NCCN Guidelines for Breast Cancer include up-to-date guidelines for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, male breast cancer, and breast cancer during pregnancy. These guidelines are developed by a multidisciplinary panel of representatives from NCCN Member Institutions with breast cancer-focused expertise in the fields of medical oncology, surgical oncology, radiation oncology, pathology, reconstructive surgery, and patient advocacy. These NCCN Guidelines Insights focus on the most recent updates to recommendations for adjuvant systemic therapy in patients with nonmetastatic, early-stage, hormone receptor-positive, HER2-negative breast cancer.

Interventions for multidimensional aspects of breast cancer-related fatigue: a meta-analytic review.

PURPOSE: This meta-analysis sought to determine whether exercise, psychological, or alternative forms of interventions differentially improve cognitive, physical, and general dimensions of cancer-related fatigue (CRF) in women with a history of breast cancer. METHODS: Databases (PubMed, PsychINFO, EMBASE, and Cochrane Library) were systematically reviewed from inception through March 2019, with data extracted from randomized controlled trials of fatigue interventions using multidimensional CRF outcome measures. Two authors independently assessed methodological quality using the Cochrane Collaboration's risk of bias tool. Analyses were performed with Comprehensive Meta-Analysis (v.3). RESULTS: A total of 471 studies were assessed, of which 11 studies with 12 sets of data involving 1067 patients were included. Across intervention types, small to moderate improvements were observed for cognitive (g = - 0.38), physical (g = - 0.46), and general (g = - 0.45) CRF (p values < 0.01). Exercise produced moderate benefit for cognitive (g = - 0.44), physical (g = - 0.48), and general (g = - 0.49) CRF (p values < 0.01) whereas psychotherapy and disparate forms of alterative interventions were not effective (p values > 0.45). However, a large effect size was observed for a single trial of acupressure across all three CRF dimensions (p < 0.05). CONCLUSIONS: Exercise improved both cognitive and physical aspects of CRF. Further studies should determine the most effective forms, duration, intensity, and methods of supporting exercise in breast cancer patients. Further investigation of acupressure as an intervention for CRF should also be considered.

Patient-reported outcomes in the Translational Breast Cancer Research Consortium.

Members of the Translational Breast Cancer Research Consortium conducted an expert-driven literature review to identify a list of domains and to evaluate potential measures of these domains for inclusion in a list of preferred measures. Measures were included if they were easily available, free of charge, and had acceptable psychometrics based on published peer-reviewed analyses. A total of 22 domains and 52 measures were identified during the selection process. Taken together, these measures form a reliable and validated list of measurement tools that are easily available and used in multiple cancer trials to assess patient-reported outcomes in relevant patients.

Clinico-pathologic features, treatment and outcomes of breast cancer during pregnancy or the post-partum period.

PURPOSE: Breast cancer during pregnancy (BC-P) or the first year post-partum (BC-PP) is rare and whether it differs from breast cancer (BC) in young women not associated with pregnancy is uncertain. METHODS: We queried our institutional database for BC-P and BC-PP cases and matched controls with BC not associated with pregnancy diagnosed between January 1, 1985 and December 31, 2013. We performed two parallel retrospective cohort studies evaluating clinico-pathologic features, treatment and outcomes for BC-P and BC-PP cases compared to their controls. RESULTS: In our population of 65 BC-P cases, 135 controls for BC-P cases, 75 BC-PP cases and 145 controls for BC-PP cases, high grade and estrogen receptor-negativity were more frequent in both case groups than their controls. Among those with stage I-III BC, patterns of local therapy were similar for both case groups and their controls, with the majority undergoing surgery and radiation. Over three-fourths of those with stage I-III BC received chemotherapy. BC-P cases tolerated chemotherapy well, with the majority receiving doxorubicin/cyclophosphamide every 3 weeks. On multivariate analyses of those with stage I-III BC, BC-P cases had non-significantly higher hazards of recurrence and death compared to their controls, while BC-PP cases had non-significantly lower hazards of recurrence and death compared to their controls. CONCLUSION: BC-P and BC-PP were associated with adverse clinic-pathologic features in our population. However, we did not observe inferior outcomes for BC-P or BC-PP compared to controls, likely due to receipt of aggressive multi-modality therapy.

Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology.

Several new systemic therapy options have become available for patients with metastatic breast cancer, which have led to improvements in survival. In addition to patient and clinical factors, the treatment selection primarily depends on the tumor biology (hormone-receptor status and HER2-status). The NCCN Guidelines specific to the workup and treatment of patients with recurrent/stage IV breast cancer are discussed in this article.

NCCN Guidelines Insights: Breast Cancer, Version 3.2018.

These NCCN Guidelines Insights highlight the updated recommendations for use of multigene assays to guide decisions on adjuvant systemic chemotherapy therapy for women with hormone receptor-positive, HER2-negative early-stage invasive breast cancer. This report summarizes these updates and discusses the rationale behind them.

Breast Cancer, Version 4.2017, NCCN Clinical Practice Guidelines in Oncology.

Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.

NCCN Guidelines Insights: Breast Cancer, Version 1.2017.

These NCCN Guidelines Insights highlight the important updates/changes to the surgical axillary staging, radiation therapy, and systemic therapy recommendations for hormone receptor-positive disease in the 1.2017 version of the NCCN Guidelines for Breast Cancer. This report summarizes these updates and discusses the rationale behind them. Updates on new drug approvals, not available at press time, can be found in the most recent version of these guidelines at NCCN.org.

Invasive Breast Cancer Version 1.2016, NCCN Clinical Practice Guidelines in Oncology.

Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The overall management of breast cancer includes the treatment of local disease with surgery, radiation therapy, or both, and the treatment of systemic disease with cytotoxic chemotherapy, endocrine therapy, biologic therapy, or combinations of these. This article outlines the NCCN Guidelines specific to breast cancer that is locoregional (restricted to one region of the body), and discusses the management of clinical stage I, II, and IIIA (T3N1M0) tumors. For NCCN Guidelines on systemic adjuvant therapy after locoregional management of clinical stage I, II and IIIA (T3N1M0) and for management for other clinical stages of breast cancer, see the complete version of these guidelines at NCCN.org.

Deleterious BRCA1/2 mutations in an urban population of Black women.

Information on the prevalence of deleterious BRCA1 and BRCA2 (BRCA1/2) mutations in clinic-based populations of Black women is limited. In order to address this gap, we performed a retrospective study to determine the prevalence of deleterious BRCA1/2 mutations, predictors of having a mutation, and acceptance of risk-reducing surgeries in Black women. In an urban unselected clinic-based population, we evaluated 211 self-identified Black women who underwent genetic counseling for hereditary breast-ovarian cancer syndrome. BRCA1/2 mutations were identified in 13.4% of the participants who received genetic testing. Younger age at diagnosis, higher BRCAPRO score, significant family history, and diagnosis of triple-negative breast cancer were associated with identification of a BRCA1/2 mutation. Of the affected patients found to have a deleterious mutation, almost half underwent prophylactic measures. In our study population, 1 in 7 Black women who underwent genetic testing harbored a deleterious BRCA1/2 mutation independent of age at diagnosis or family history.

NCCN Guidelines Insights Breast Cancer, Version 1.2016.

These NCCN Guideline Insights highlight the important updates to the systemic therapy recommendations in the 2016 NCCN Guidelines for Breast Cancer. In the most recent version of these guidelines, the NCCN Breast Cancer Panel included a new section on the principles of preoperative systemic therapy. In addition, based on new evidence, the panel updated systemic therapy recommendations for women with hormone receptor-positive breast cancer in the adjuvant and metastatic disease settings and for patients with HER2-positive metastatic breast cancer. This report summarizes these recent updates and discusses the rationale behind them.

Breast Cancer Version 2.2015.

Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The overall management of breast cancer includes the treatment of local disease with surgery, radiation therapy, or both, and the treatment of systemic disease with cytotoxic chemotherapy, endocrine therapy, biologic therapy, or combinations of these. This portion of the NCCN Guidelines discusses recommendations specific to the locoregional management of clinical stage I, II, and IIIA (T3N1M0) tumors.

TBCRC 057: Survey about willingness to participate in cancer clinical trials during the pandemic.

BACKGROUND: Breast cancer patients experienced heightened anxiety during the pandemic. Also, modifications to clinical trial activities allowing for virtual platforms, local assessments, and greater flexibility were introduced to facilitate participation. We sought to evaluate the association between pandemic-related anxiety and willingness to participate in trials and how pandemic-era modifications to trial activities affect the decision to participate. METHODS: We conducted an online survey from August to September, 2021 of patients with breast cancer assessing pandemic-related anxiety; clinical trials knowledge and attitudes; willingness to participate during and before the pandemic; and how each modification affects the decision to participate. Fisher's exact tests evaluated differences in proportions and two-sample t-tests evaluated differences in means. The association of pandemic-related anxiety with a decline in willingness to participate during compared to prior to the pandemic was modeled using logistic regression. RESULTS: Among 385 respondents who completed the survey, 81% reported moderate-severe pandemic-related anxiety. Mean willingness to participate in a trial was lower during the pandemic than prior [2.97 (SD 1.17) vs. 3.10 (SD 1.09), (p < 0.001)]. Severe anxiety was associated with higher odds of diminished willingness to participate during the pandemic compared to prior (OR 5.07). Each of the modifications, with the exception of opting out of research-only blood tests, were endorsed by >50% of respondents as strategies that would increase their likelihood of deciding to participate. CONCLUSIONS: While pandemic-related anxiety was associated with diminished willingness to participate in trials, the leading reasons for reluctance to consider trial participation were unrelated to the pandemic but included worries about not getting the best treatment, side effects, and delaying care. Patients view trial modifications favorably, supporting continuation of these modifications, as endorsed by the National Cancer Institute and others.

Adjuvant treatment decisions among adults aged 65 years and older with early-stage hormone receptor positive breast cancer seen in a simple multidisciplinary clinic versus standard consultation.

INTRODUCTION: Randomized studies support de-escalation of adjuvant therapy for a target population of older adults ≥65 years with stage I, estrogen-receptor (ER) positive breast cancer after breast conserving surgery. We sought to evaluate the impact of a simplified multidisciplinary clinic (s-MDC) in this population by comparing treatment patterns and patient perceptions of adjuvant radiation therapy (RT) and hormone therapy (HT) between patients seen in s-MDC vs. standard consultations. MATERIALS AND METHODS: Medical records were retrospectively reviewed for patients in the above target population who underwent surgery between August 2020 and May 2022 at our institution. Two cohorts were included: (1) patients seen in s-MDC, and (2) patients seen in standard clinic separately by medical and radiation oncology (non-s-MDC cohort). The non-s-MDC patients declined, could not attend, and/or were not referred to the s-MDC. Patients in the s-MDC cohort were prospectively administered validated questionnaires to evaluate patient reported data including the Decision Autonomy Preference Scale (DAPS), e-Prognosis, and Medical Maximizing-Minimizing Scale (MMS). Chi square, t-tests, and non-parametric equivalents compared demographics, and logistic regression evaluated RT and HT use and survey score outcomes between cohorts. RESULTS: A total of 127 patients met inclusion criteria, with 33 s-MDC and 94 non-s-MDC patients. There was no difference between the cohorts in age, margin status, histology, grade, or focality. In the s-MDC cohort there were significantly more patients without sentinel lymph node biopsy (71.3% vs 42.4%, p = 0.003) and mean tumor size was smaller (0.69 vs. 0.96 cm, p < 0.003), and Charlson comborbidity index (CCI) was higher (5.21 vs 4.96, p = 0.038). There was no significant difference in receipt of RT (65% s-MDC vs 77% standard; odds ratio [OR] = 0.55, p = 0.189), HT (78% ss-MDC vs 72% standard; OR = 1.36, p = 0.513), or both (50% s-MDC vs 59% standard; OR = 0.7, p = 0.429). The s-MDC cohort was significantly more likely to undergo accelerated (vs. standard hypofractionated) RT (70% vs 39%; OR = 3.59, p = 0.020). In s-MDC patients with completed questionnaires (n = 33), all whose selected "mostly patient (n=6)" based decision making by DAPS chose RT while all "mostly doctor (n=1)" chose no RT. Based on e-Prognosis, there were lower odds of RT for increasing Schonberg score/ higher 10 yr mortality risk (OR 0.600, p = 0.048). MMS score ≥ 40 ("maximizer") was strongly linked with the use of RT (OR 18.57, p = 0.011). DISCUSSION: For adults ≥65 years with early stage, ER positive breast cancer, s-MDC participation was not significantly associated with lower use of adjuvant RT or HT versus standard consultation but was significantly associated with shorter RT courses. DAPS and MMS results indicate that patient treatment preference may be predictable, highlighting an opportunity to tailor consultation discussions and recommendations based on intrinsic patient preferences and individual goals.

Factors associated with weight gain in pre- and post-menopausal women receiving adjuvant endocrine therapy for breast cancer.

PURPOSE: Weight gain after breast cancer poses health risks. We aimed to identify factors associated with weight gain during adjuvant endocrine therapy (AET). METHODS: Women initiating AET enrolled in a prospective cohort. Participants completed FACT-ES plus PROMIS pain interference, depression, anxiety, fatigue, sleep disturbance and physical function measures at baseline, 3, 6, 12, 24, 36, 48 and 60 months. Treatment-emergent symptoms were defined as changes in scores in the direction indicative of worsening symptoms that exceeded the minimal important difference at 3 and/or 6 months compared to baseline. We used logistic regression to evaluate associations of clinicodemographic features and treatment-emergent symptoms with clinically significant weight gain over 60 months (defined as ≥ 5% compared to baseline) in pre- and post-menopausal participants. RESULTS: Of 309 participants, 99 (32%) were pre-menopausal. The 60 months cumulative incidence of clinically significant weight gain was greater in pre- than post-menopausal participants (67% vs 43%, p < 0.001). Among pre-menopausal participants, treatment-emergent pain interference (OR 2.49), aromatase inhibitor receipt (OR 2.8), mastectomy, (OR 2.06) and White race (OR 7.13) were associated with weight gain. Among post-menopausal participants, treatment-emergent endocrine symptoms (OR 2.86), higher stage (OR 2.25) and White race (OR 2.29) were associated with weight gain while treatment-emergent physical function decline (OR 0.30) was associated with lower likelihood of weight gain. CONCLUSIONS: Weight gain during AET is common, especially for pre-menopausal women. Clinicodemographic features and early treatment-emergent symptoms may identify at risk individuals. IMPLICATIONS FOR CANCER SURVIVORS: Patients at risk for weight gain can be identified early during AET. GOV IDENTIFIER: NCT01937052, registered September 3, 2013.

Feasibility of Symptom Monitoring During the First Year of Endocrine Therapy for Early Breast Cancer Using Patient-Reported Outcomes Collected via Smartphone App.

PURPOSE: Treatment-associated symptoms drive early discontinuation of adjuvant endocrine therapy (ET) for breast cancer. We hypothesized that symptom monitoring with electronic patient-reported outcomes (ePROs) during adjuvant ET will enhance symptom detection, symptom management, and persistence. METHODS: Eligible patients were initiating ET for stage 0-III breast cancer. Participants completed ePRO surveys via smartphone at baseline and 1, 3, 6, and 12 months. Measures included Patient-Reported Outcomes Measurement Information System Anxiety, Depression, Fatigue, and Vaginal Discomfort; plus Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events items assessing joint pain, hot flashes, vaginal dryness, concentration problems, and memory problems. Scores surpassing prespecified thresholds triggered alerts, and recommended symptom management pathways were provided to clinicians. The primary objective was to evaluate feasibility, assessed by survey completion rates, with targets of >65% for the baseline survey and ≥1 follow-up survey during the first 6 months. Secondary objectives included 12-month ET discontinuation rate (target: ≤15%), describing symptoms and evaluating pathway implementation. RESULTS: Among 250 participants, 73.2% completed the baseline survey and 69.6% completed ≥1 follow-up survey during the first 6 months. Thirty-one percent of participants had ≥1 symptom alert at baseline and 74% had ≥1 symptom alert during follow-up. The proportions of participants for whom pathway-concordant symptom management was documented at each time point ranged from 12.8% to 36.6%. Twenty-eight participants (11.2%) discontinued ET by 12 months. CONCLUSION: Symptom monitoring with ePROs during adjuvant ET is feasible. Despite infrequent documentation of pathway-concordant symptom management after symptom alerts, ePROs were associated with favorable short-term ET persistence.