The POWER-PAK Score Characterizes Tumor Response to 3 Months of Preoperative Endocrine Therapy.

BACKGROUND: The Pre-Operative Window of Endocrine Therapy to Inform Radiation Therapy Decisions (POWER, NCT04272801) trial aims to determine whether 3 months of preoperative endocrine therapy (pre-ET) informs adjuvant radiation therapy decisions among older women with early stage, ER-positive breast cancer. We propose the POWER Pathologic Assessment and Ki-67 (POWER-PAK) scoring system to characterize the histologic effects of pre-ET. METHODS: Histologic evaluation was performed on core biopsy and lumpectomy specimens from 37 POWER trial participants who completed pre-ET and surgery. The POWER-PAK score consists of tumor regression, decrease in Ki-67 expression, and ER expression, each ranging from 0 to 2. Scores were aggregated to create the POWER-PAK score with a range from 0 to 6. Participants with no residual tumor were labelled 6-NRT. RESULTS: ER expression did not decrease after pre-ET. Ki-67 decreased from 13% in biopsy specimens to 5% in the lumpectomy specimens (p < 0.001). Cellularity decreased from 40% to 23% (p < 0.001). There was heterogeneity of POWER-PAK scores ranging from 2 to 6-NRT: score of 2, n = 2 (5.4%); 4, n = 8 (21.6%); 5, n = 4 (10.8%); 6, n = 16 (43.2%); and 6-NRT, n = 7 (18.9%). Participants with a score ≥ 5 were more likely to have smaller tumors after pre-ET compared with those with a score < 5 (p = 0.04). CONCLUSIONS: The tumor responses following treatment with pre-ET are heterogenous. We propose that the POWER-PAK scoring system can be used to quantify response to pre-ET. Future studies will explore the use of POWER-PAK to support informed decision-making for adjuvant therapy options for older women with early stage breast cancer.

Long-Term Adherence to Adjuvant Endocrine Therapy Following Various Radiotherapy Modalities in Early Stage Hormone Receptor Positive Breast Cancer.

INTRODUCTION: We compared the rates of long-term adjuvant endocrine therapy (AET) adherence after various radiation therapy (RT) modalities among patients with early stage breast cancer. MATERIALS AND METHODS: Medical records from patients with stage 0, I, or IIA (tumors ≤3 cm), hormone receptor (HR) positive breast cancer that received adjuvant radiation therapy (RT) from 2013 to 2015 at a single institution were retrospectively reviewed. All patients received breast conserving surgery (BCS) followed by adjuvant RT via one of the following modalities: whole breast radiotherapy (WBI), partial breast irradiation (PBI) with either external beam radiation therapy (EBRT) or fractionated intracavitary high-dose rate (HDR) brachytherapy, or single fraction HDR-brachytherapy intraoperative-radiation therapy (IORT). RESULTS: One hundred fourteen patients were reviewed. Thirty patients received WBI, 41 PBI, and 43 IORT with a median follow up of 64.2, 72.0, and 58.6 months, respectively. For the entire cohort, AET adherence was approximately 64% at 2 years and 56% at 5 years. Among patients in the IORT clinical trial, adherence to AET was approximately 51% at 2 years and 40% at 5 years. After controlling for additional factors, DCIS histology (vs invasive disease) and IORT (compared to other radiation modalities) were associated with decreased endocrine therapy adherence (P < 0.05). CONCLUSION: DCIS histology and receipt of IORT were associated with lower rates of adherence to AET at 5 years. Our findings suggest that examination of the efficacy of RT interventions such as PBI and IORT in patients who do not receive AET is warranted.

Including partners in discussions of sexual side effects from breast cancer: a qualitative study of survivors, partners, and providers.

PURPOSE: Ensuring there are clear standards for addressing cancer-related sexual side effects is important. Currently, there are differences in two leading sets of clinical guidelines regarding the inclusion of survivors' romantic partners into clinical discussions between survivors and their providers about this issue. To help refine guidelines, we examine breast cancer survivor, partner, and oncology provider perspectives about including partners in discussions about cancer-related sexual side effects in a secondary analysis of a broader qualitative study. METHODS: Partnered female breast cancer survivors (N = 29) completed online surveys, and intimate partners of breast cancer survivors (N = 12) and breast oncology providers (N = 8) completed semi-structured interviews. Themes were derived from thematic content analysis. RESULTS: Among survivors who reported a discussion with their provider, fewer than half indicated their partner had been present, despite most survivors expressing it was - or would have been - helpful to include their partner. Partners also largely indicated being included was or would have been helpful, when welcomed by the survivor. Providers similarly emphasized the importance of survivors' autonomy in deciding whether to discuss sexual concerns in the presence of a partner. CONCLUSIONS: Partners were infrequently included in conversations about cancer-related sexual side effects, even though survivors, partners, and providers alike expressed value in these discussions occurring with the couple together - when that is the survivor's preference. Findings suggest future clinical guidelines should emphasize that incorporating partners into clinical discussions about sexual concerns is important for many breast cancer patients. Soliciting and enacting patients' preferences is essential for truly patient-centered care.

Addressing sexual concerns of female breast cancer survivors and partners: a qualitative study of survivors, partners, and oncology providers about Internet intervention preferences.

PURPOSE: Sexual side effects after breast cancer treatment are common and distressing to both survivors and their intimate partners, yet few receive interventions to address cancer-related sexual concerns. To direct intervention development, this qualitative study assessed the perceptions of female breast cancer survivors, intimate partners of breast cancer survivors, and breast cancer oncology providers about how an Internet intervention for couples may address breast cancer-related sexual concerns. METHODS: Survivors (N = 20) responded to online open-ended surveys. Partners (N = 12) and providers (N = 8) completed individual semi-structured interviews. Data were inductively coded using thematic content analysis. RESULTS: Three primary intervention content areas were identified by the key stakeholder groups: (1) information about and strategies to manage physical and psychological effects of cancer treatment on sexual health, (2) relationship and communication support, and (3) addressing bodily changes and self-image after treatment. Survivors and partners tended to express interest in some individualized intervention private from their partner, although they also emphasized the importance of opening communication about sexual concerns within the couple. Survivors and partners expressed interest in an intervention that addresses changing needs across the cancer trajectory, available from the time of diagnosis and through survivorship. CONCLUSION: Internet intervention for couples to address cancer-related sexual concerns, particularly one that provides basic education about treatment side effects and that evolves with couples' changing needs across the cancer trajectory, was perceived as a valuable addition to breast cancer care by survivors, partners, and providers.

Efficient dose-finding for drug combination studies involving a shift in study populations.

This paper describes the design of an early phase, prospective trial evaluating the safety and tolerability of the combination of the histone deacetylase inhibitor, entinostat, in combination with capecitabine. The study consists of two parts; an initial phase evaluating the safety of the combination in participants with metastatic breast cancer, followed by a second phase assessing the safety of the combination in participants with residual disease after neo-adjuvant chemotherapy for breast cancer. We describe the adaptation of a model-based design for identifying the maximum tolerated dose combination that efficiently moves from the initial phase in an advanced disease population to the second phase in the target population. Operating characteristics demonstrate the ability of the method to accurately predict true maximum tolerated dose combinations in a high percentage of trials with reasonable sample sizes, while treating participants at and around desirable combinations. The proposed design is a practical, early-phase, adaptive method for use with drug combination dose finding in the presence of shifting patient populations. More challenging research questions are being investigated in early-phase trials, which has created the need to implement more flexible designs that can meet the objectives of current studies, such as those exploring drug combinations while addressing patient heterogeneity. Our goal is to facilitate acceptance and application of more novel designs in contemporary early-phase studies.