Pregnancy After Breast Cancer in Young BRCA Carriers: An International Hospital-Based Cohort Study.

Importance: Young women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers. Objective: To investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers. Design, Setting, and Participants: International, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023. Exposure: Pregnancy after breast cancer. Main Outcomes and Measures: Primary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer-specific survival, overall survival, pregnancy, and fetal and obstetric outcomes. Results: Of 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (≥37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer-specific survival and overall survival. Conclusions and Relevance: In this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03673306.

NCCN Guidelines® Insights: Survivorship, Version 1.2023.

The NCCN Guidelines for Survivorship are intended to help healthcare professionals address the complex and varied needs of cancer survivors. The NCCN Guidelines provide screening, evaluation, and treatment recommendations for psychosocial and physical problems resulting from adult-onset cancer and its treatment; recommendations to help promote healthy behaviors and immunizations in survivors; and a framework for care coordination. These NCCN Guidelines Insights summarize recent guideline updates and panel discussions pertaining to sleep disorders, fatigue, and cognitive function in cancer survivors.

Association of body composition and surgical outcomes in patients with early-stage breast cancer.

BACKGROUND: Breast cancer is a disease that requires multimodality treatment, and surgical resection of the tumor is a critical component of curative intent treatment. Obesity, defined as a body mass index (BMI) > 30, has been associated with increased surgical complications. Additionally, sarcopenia, a condition of gradual loss of muscle mass, has been associated with worse breast cancer treatment outcomes. Sarcopenia occurs with increased age, inactivity, and poor diet leading to patient frailty, which can increase medical treatment complications. Even patients with high BMI can have sarcopenia (termed sarcopenic obesity). We investigated the association of sarcopenia with surgical complications for breast cancer. METHODS: A retrospective review was performed of patients diagnosed with breast cancer who received bioelectrical impedance spectrometry analysis of skeletal muscle mass and had surgery at our institution. Patient characteristics, treatment data, surgical type and complications were obtained from medical records. Multivariate logistic regression models were used to associate sarcopenia status and BMI with surgical complications, adjusted for other patient characteristics. RESULTS: We analyzed 682 patients with stage I to III breast cancer. On multivariable logistic regression controlling for age, BMI, comorbidities, and types of surgeries (lumpectomy, mastectomy with or without reconstruction), sarcopenia (p = 0.66) was not associated with surgical complications. Obesity was associated with a higher rate of surgical complications in patients who received mastectomy with reconstruction (p = 0.01). More complex surgical approaches were associated with a higher risk of surgical complications in our series. CONCLUSION: Compared with those undergoing lumpectomy or mastectomy without reconstruction, patients undergoing mastectomy with reconstruction were more likely to experience postoperative complications and obesity was associated with higher risk of complication in the latter group. We did not identify a correlation between sarcopenia and rate of adverse surgical outcomes.

Cell State and Cell Type: Deconvoluting Circulating Tumor Cell Populations in Liquid Biopsies by Multi-Omics.

Bi-directional crosstalk between the tumor and the tumor microenvironment (TME) has been shown to increase the rate of tumor evolution and to play a key role in neoplastic progression, therapeutic resistance, and a patient's overall survival. Here, we set out to use a comprehensive liquid-biopsy analysis to study cancer and specific TME cells in circulation and their association with disease status. Cytokeratin+, CD45- circulating rare cells (CRCs) from nine breast and four prostate cancer patients were characterized through morphometrics, single-cell copy number analysis, and targeted multiplexed proteomics to delineate cancer cell lineage from other rare cells originating in the TME. We show that we can detect epithelial circulating tumor cells (EPI.CTC), CTCs undergoing epithelial-to-mesenchymal transition (EMT.CTC) and circulating endothelial cells (CECs) using a universal rare event detection platform (HDSCA). Longitudinal analysis of an index patient finds that CTCs are present at the time of disease progression, while CECs are predominately present at the time of stable disease. In a small cohort of prostate and breast cancer patients, we find high inter-patient and temporal intra-patient variability in the expression of tissue specific markers such as ER, HER2, AR, PSA and PSMA and EpCAM. Our study stresses the importance of the multi-omic characterization of circulating rare cells in patients with breast and prostate carcinomas, specifically highlighting overlapping and cell type defining proteo-genomic characteristics of CTCs and CECs.

Operational Metrics for the ELAINE 2 Study Combining a Traditional Approach With a Just-in-TIME Model.

PURPOSE: There are numerous barriers to enrollment in oncology biomarker-driven studies. METHODS: The ELAINE 2 study (ClinicalTrials.gov identifier: NCT04432454) is an open-label phase 2 study of lasofoxifene combined with abemaciclib in patients with advanced or metastatic estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer with an ESR1 mutation. ELAINE 2 opened clinical sites by using a Traditional approach, which activated a site before patient identification, and the Tempus TIME Trial network, which opened a site only after identifying an eligible patient. This manuscript presents the operational metrics comparing the Traditional and TIME Trial site data. RESULTS: The study enrolled patients over 34 weeks and 16 sites (six Traditional and 10 TIME Trial) participated. Duration for full clinical trial agreement execution for Traditional sites and TIME Trial sites averaged 200.5 (range, 142-257) and 7.6 days (range, 2-14), respectively. Institutional review board approval time for Traditional sites and TIME Trial sites was 27.5 (range, 12-71) and 3.0 days (range, 1-12), respectively. Duration from study activation to first consent was 33.3 (range, 18-58) and 8.8 days (range, 1-35) for Traditional and TIME Trial sites, respectively. The first patient on study was at a TIME Trial site 115 days before a Traditional site and the first seven patients enrolled were at TIME Trial sites. Traditional sites consented 23 and enrolled 16 patients, while TIME Trial sites consented 16 and enrolled 13. The trial enrolled 29 patients in 8.5 months with the anticipated enrollment duration being 12-18 months. CONCLUSION: The TIME Trial network opened earlier and enrolled the first study patients. These results demonstrate that the Just-in-TIME model, along with a Traditional model, can improve enrollment in biomarker-driven studies.

Interrupting Endocrine Therapy to Attempt Pregnancy after Breast Cancer.

BACKGROUND: Prospective data on the risk of recurrence among women with hormone receptor-positive early breast cancer who temporarily discontinue endocrine therapy to attempt pregnancy are lacking. METHODS: We conducted a single-group trial in which we evaluated the temporary interruption of adjuvant endocrine therapy to attempt pregnancy in young women with previous breast cancer. Eligible women were 42 years of age or younger; had had stage I, II, or III disease; had received adjuvant endocrine therapy for 18 to 30 months; and desired pregnancy. The primary end point was the number of breast cancer events (defined as local, regional, or distant recurrence of invasive breast cancer or new contralateral invasive breast cancer) during follow-up. The primary analysis was planned to be performed after 1600 patient-years of follow-up. The prespecified safety threshold was the occurrence of 46 breast cancer events during this period. Breast cancer outcomes in this treatment-interruption group were compared with those in an external control cohort consisting of women who would have met the entry criteria for the current trial. RESULTS: Among 516 women, the median age was 37 years, the median time from breast cancer diagnosis to enrollment was 29 months, and 93.4% had stage I or II disease. Among 497 women who were followed for pregnancy status, 368 (74.0%) had at least one pregnancy and 317 (63.8%) had at least one live birth. In total, 365 babies were born. At 1638 patient-years of follow-up (median follow-up, 41 months), 44 patients had a breast cancer event, a result that did not exceed the safety threshold. The 3-year incidence of breast cancer events was 8.9% (95% confidence interval [CI], 6.3 to 11.6) in the treatment-interruption group and 9.2% (95% CI, 7.6 to 10.8) in the control cohort. CONCLUSIONS: Among select women with previous hormone receptor-positive early breast cancer, temporary interruption of endocrine therapy to attempt pregnancy did not confer a greater short-term risk of breast cancer events, including distant recurrence, than that in the external control cohort. Further follow-up is critical to inform longer-term safety. (Funded by ETOP IBCSG Partners Foundation and others; POSITIVE ClinicalTrials.gov number, NCT02308085.).

Adherence to Cancer Prevention Lifestyle Recommendations Before, During, and 2 Years After Treatment for High-risk Breast Cancer.

Importance: The American Institute for Cancer Research and American Cancer Society regularly publish modifiable lifestyle recommendations for cancer prevention. Whether these recommendations have an impact on high-risk breast cancer survival remains unknown. Objective: To investigate whether adherence to cancer prevention recommendations before, during, and 1 and 2 years after breast cancer treatment was associated with disease recurrence or mortality. Design, Setting, and Participants: The Diet, Exercise, Lifestyles, and Cancer Prognosis Study (DELCaP) was a prospective, observational cohort study designed to assess lifestyles before diagnosis, during treatment, and at 1 and 2 years after treatment completion, implemented ancillary to the Southwest Oncology Group (SWOG) S0221 trial, a multicenter trial that compared chemotherapy regimens in breast cancer. Participants were chemotherapy-naive patients with pathologic stage I to III high-risk breast cancer, defined as node-positive disease with hormone receptor-negative tumors larger than 1 cm or any tumor larger than 2 cm. Patients with poor performance status and comorbidities were excluded from S0221. The study was conducted from January 1, 2005, to December 31, 2010; mean (SD) follow-up time for those not experiencing an event was 7.7 (2.1) years through December 31, 2018. The analyses reported herein were performed from March 2022 to January 2023. Exposure: An aggregated lifestyle index score comprising data from 4 time points and 7 lifestyles, including (1) physical activity, (2) body mass index, (3) fruit and vegetable consumption, (4) red and processed meat intake, (5) sugar-sweetened beverage consumption, (6) alcohol consumption, and (7) smoking. Higher scores indicated healthier lifestyle. Main Outcomes and Measures: Disease recurrence and all-cause mortality. Results: A total of 1340 women (mean [SD] age, 51.3 [9.9] years) completed the baseline questionnaire. Most patients were diagnosed with hormone-receptor positive breast cancer (873 [65.3%]) and completed some education beyond high school (954 [71.2%]). In time-dependent multivariable analyses, patients with highest vs lowest lifestyle index scores experienced a 37.0% reduction in disease recurrence (hazard ratio, 0.63; 95% CI, 0.48-0.82) and a 58.0% reduction in mortality (hazard ratio, 0.42; 95% CI, 0.30-0.59). Conclusions and Relevance: In this observational study of patients with high-risk breast cancer, strongest collective adherence to cancer prevention lifestyle recommendations was associated with significant reductions in disease recurrence and mortality. Education and implementation strategies to help patients adhere to cancer prevention recommendations throughout the cancer care continuum may be warranted in breast cancer.

Sarcopenia detected with bioelectrical impedance versus CT scan and chemotherapy tolerance in patients with early breast cancer.

BACKGROUND: Early breast cancer (EBC) is a potentially curable disease. Some patients with EBC require chemotherapy, exposing patients to undesirable side effects. Loss of muscle mass, or sarcopenia, has been associated with worse outcomes in patients with EBC and worse treatment-related toxicity in patients with advanced breast cancer. CT scans can identify sarcopenia; however, most patients with EBC do not require routine CT scans. Bioelectrical impedance spectrometry (BIS) is another method to detect sarcopenia and can be performed quickly in the office without radiation exposure. We sought to investigate whether sarcopenia measurements by CT scan versus BIS correlated with each other and whether sarcopenia identified by each method is associated with chemotherapy toxicity and adherence in patients with EBC. METHODS: This is a retrospective study; eligible patients received chemotherapy treatment for EBC and had undergone BIS. A subset of patients had also had a CT abdomen with a Lumbar L3 level. Measures of sarcopenia were obtained from the BIS and CT data. In addition, patient characteristics, treatment, and toxicity-related outcomes were obtained from medical records. Multivariate logistic regression models were used to associate sarcopenia status with toxicity endpoints, adjusted for other patient characteristics. RESULTS: There was a moderate correlation between sarcopenia detected by CT scan and BIS (r = 0.64 p < 0.0001). Patients with sarcopenia detected by BIS had more chemotherapy toxicity (OR = 2.56; CI 1.72-3.84), dose reductions or dose delays (OR = 1.58; CI 1.06-2.38), and hospitalizations (OR = 2.38; CI 1.33-4.16) due to side effects than patients without sarcopenia. CONCLUSION: The presence of sarcopenia in patients with EBC is associated with worse chemotherapy tolerance. BIS represents a high-value alternative to CT scans for sarcopenia assessment.

NCCN Guidelines® Insights: Survivorship, Version 1.2022.

The NCCN Guidelines for Survivorship are intended to help healthcare professionals who work with survivors to ensure that the survivors' complex and varied needs are addressed. The NCCN Guidelines provide screening, evaluation, and treatment recommendations for the consequences of adult-onset cancer and its treatment; recommendations to help promote physical activity, weight management, and immunizations in survivors; and a framework for care coordination. This article summarizes updates to the NCCN Guidelines pertaining to preventive health for cancer survivors, including recommendations about alcohol consumption and vaccinations.

Association of sarcopenia with endocrine therapy toxicity in patients with early breast cancer.

BACKGROUND: Endocrine therapy reduces recurrence risk and improves survival in women with hormone receptor-positive breast cancer; however, side effects can decrease quality of life, leading to reduced treatment adherence. Sarcopenia is the loss of skeletal muscle mass that happens with age; it is associated with worse survival and reduced chemotherapy adherence in patients with breast cancer. The impact of sarcopenia on endocrine therapy tolerance has not been investigated. The current study evaluates the associations of sarcopenia with endocrine therapy toxicity and treatment tolerance. METHODS: Skeletal muscle mass was measured by bioelectrical impedance spectrometry. Skeletal muscle index (SMI) was calculated to assess for sarcopenia: SMI = (SMM kg)/(patient height, m2). Patients with SMI ≤ 6.75 kg/m2 were considered sarcopenic. A chart review was performed to obtain patient characteristics, endocrine therapy toxicity, and early treatment change or termination. Fisher's exact test was performed to associate patient characteristics and outcomes with sarcopenia status. RESULTS: Four hundred eighty-two patients with stage I-III breast cancer were prescribed endocrine therapy and had undergone sarcopenia evaluation. The median age was 61 years (29-88 years). Sarcopenia was identified in 35% of patients. Twelve percent of patients experienced grade 3-4 endocrine-related toxicities. On multivariable logistic analysis, sarcopenia was associated with increased odds of experiencing endocrine-related side effects (p = 0.006). In addition, patients with sarcopenia stopped or changed their medication due to side effects more often than those without sarcopenia (p = 0.03). CONCLUSION: The presence of sarcopenia in patients with EBC represents a potentially modifiable risk factor for more significant endocrine therapy side effects and reduced treatment tolerance.

Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer.

BACKGROUND: Among breast cancers without human epidermal growth factor receptor 2 (HER2) amplification, overexpression, or both, a large proportion express low levels of HER2 that may be targetable. Currently available HER2-directed therapies have been ineffective in patients with these "HER2-low" cancers. METHODS: We conducted a phase 3 trial involving patients with HER2-low metastatic breast cancer who had received one or two previous lines of chemotherapy. (Low expression of HER2 was defined as a score of 1+ on immunohistochemical [IHC] analysis or as an IHC score of 2+ and negative results on in situ hybridization.) Patients were randomly assigned in a 2:1 ratio to receive trastuzumab deruxtecan or the physician's choice of chemotherapy. The primary end point was progression-free survival in the hormone receptor-positive cohort. The key secondary end points were progression-free survival among all patients and overall survival in the hormone receptor-positive cohort and among all patients. RESULTS: Of 557 patients who underwent randomization, 494 (88.7%) had hormone receptor-positive disease and 63 (11.3%) had hormone receptor-negative disease. In the hormone receptor-positive cohort, the median progression-free survival was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician's choice group (hazard ratio for disease progression or death, 0.51; P<0.001), and overall survival was 23.9 months and 17.5 months, respectively (hazard ratio for death, 0.64; P = 0.003). Among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician's choice group (hazard ratio for disease progression or death, 0.50; P<0.001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P = 0.001). Adverse events of grade 3 or higher occurred in 52.6% of the patients who received trastuzumab deruxtecan and 67.4% of those who received the physician's choice of chemotherapy. Adjudicated, drug-related interstitial lung disease or pneumonitis occurred in 12.1% of the patients who received trastuzumab deruxtecan; 0.8% had grade 5 events. CONCLUSIONS: In this trial involving patients with HER2-low metastatic breast cancer, trastuzumab deruxtecan resulted in significantly longer progression-free and overall survival than the physician's choice of chemotherapy. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast04 ClinicalTrials.gov number, NCT03734029.).

A randomized controlled trial of the effect of supervised exercise on functional outcomes in older African American and non-Hispanic White breast cancer survivors: Are there racial differences in the effects of exercise on functional outcomes?

BACKGROUND: The objective of this study was to test the hypothesis that exercise would be more effective than a support group plus Fitbit (SG+Fitbit) program in improving functional outcomes in older breast cancer survivors (BCSs) and that race would moderate the exercise effect on outcomes. METHODS: Older African American (AA) and non-Hispanic White (NHW) BCSs were purposively recruited and enrolled into the 52-week randomized controlled trial. The interventions included 20 weeks of supervised moderate-intensity aerobic and resistance training followed by 32 weeks of unsupervised exercise called IMPROVE (n = 108) and a 20-week SG+Fitbit program followed by 32 weeks of unsupervised activity (n = 105). Study outcomes were assessed at 20 and 52 weeks. The primary outcome was the change in Short Physical Performance Battery (SPPB) scores 20 weeks from the baseline between arms. Secondary outcomes included change in the 6-Minute Walk Test (6MWT) in meters 20 weeks from the baseline between arms. General linear regression and multivariable logistic regression analyses were used. RESULTS: The mean age was 71.9 years (SD, 5.9 years), and 44% were AA. SPPB scores did not differ between arms (adjusted difference in mean change, 0.13; 95% CI, -0.28 to 0.55; P = .53). However, the exercise arm (vs the SG+Fitbit arm) improved on the 6MWT (21.6 m; 95% CI, 2.5-40.6 m; P = .03). Race moderated the exercise effect on the 6MWT (adjusted interaction effect, 43.3 m; 95% CI, 6.3-80.2 m; P = .02); this implied that the change in the adjusted mean for the 6MWT at 20 weeks from the baseline was 43.3 m higher in AA exercise participants versus NHW exercise participants. CONCLUSIONS: Combined aerobic and resistance exercise appears to improve physical performance in older BCSs, and the exercise effect might be moderated by race, with AAs appearing to derive larger benefits in comparison with NHWs. Larger studies are warranted to confirm the study findings.

Real-World Outcomes of Everolimus and Exemestane for the Treatment of Metastatic Hormone Receptor-Positive Breast Cancer in Patients Previously Treated With CDK4/6 Inhibitors.

PURPOSE: Everolimus with exemestane (EVE+EXE) was FDA-approved to treat metastatic hormone receptor-positive breast cancer (mHRBC) based on BOLERO-2. However, none of those patients received prior CDK4/6 inhibitors. The purpose of this study is to evaluate the efficacy of EVE+EXE in mHRBC after CDK4/6 inhibitors. METHODS: A retrospective review of patients ≥18 years old with mHRBC treated with EVE+EXE, for ≥30 days, at our institution from January 1, 2012, to April 1, 2020 was conducted. Primary objective was to compare progression free survival (PFS) for EVE+EXE between patients with and without prior exposure to CDK4/6 inhibitors. Secondary outcomes included overall survival and safety. RESULTS: 192 patients were included in the study (n = 79, prior CDK4/6 inhibitor use; n = 113, no prior CDK4/6 inhibitor use). Baseline patient characteristics were similar between groups. Greater number of prior therapies before EVE+EXE use increased risk of disease progression (P = .017). Patients with prior CDK4/6 inhibitor use had a lower median PFS of 3.8 months (95% CI: 3.4-4.7) vs. 5.4 months (95% CI: 3.9-6.2) for patients without prior CDK4/6 inhibitor use, with a HR for progression of 1.46 (95% CI: 1.08 to 1.97, P = .013). Overall survival between groups was not significantly different. CONCLUSION: Patients who received a prior CDK4/6 inhibitor had a lower median PFS benefit from EVE+EXE compared to those who did not, without differences in overall survival. Although PFS is expected to decrease with subsequent lines of therapy, it is reasonable to use EVE+EXE after CDK4/6 inhibitors in selected patients, recognizing that additional benefit is modest.

A Randomized Trial of Fulvestrant, Everolimus, and Anastrozole for the Front-line Treatment of Patients with Advanced Hormone Receptor-positive Breast Cancer, SWOG S1222.

PURPOSE: Metastatic hormone receptor (HR)-positive, HER2-negative breast cancer is an important cause of cancer mortality. Endocrine treatment with or without additional targeted therapies has been the mainstay of treatment. This trial was designed to evaluate the combination of fulvestrant plus everolimus versus fulvestrant, everolimus, and anastrozole compared with fulvestrant alone in the first-line treatment of advanced HR-positive, HER2-negative breast cancer. PATIENTS AND METHODS: This randomized placebo-controlled trial included postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had received no prior systemic therapy for metastatic disease. Participants were randomized to one of three treatment arms and the primary outcome was progression-free survival (PFS), comparing combinations of fulvestrant and everolimus with or without anastrozole with fulvestrant alone. Circulating tumor cells (CTC), as measured with two different methods, and circulating tumor DNA (ctDNA) were evaluated serially prior to treatment and the beginning of the second cycle of therapy. RESULTS: Due in part to changes in clinical practice, the study was closed after accruing only 37 participants. There was no evidence that everolimus-containing combination treatment improved PFS or overall survival relative to fulvestrant alone. When modeled continuously, an association was observed of baseline CTC and ctDNA with poorer survival. CONCLUSIONS: Although power of the study was limited, the findings were unable to support the routine use of everolimus combination endocrine therapy in the first-line treatment of advanced hormone-sensitive breast cancer. Prognostic impact of baseline ctDNA and copy-number variations in CTC was demonstrated.

Management of Diarrhea in Patients with HER2-Positive Breast Cancer Treated with Neratinib: A Case Series and Summary of the Literature.

INTRODUCTION: Neratinib and neratinib-based combinations have demonstrated efficacy for treatment of human epidermal growth factor receptor 2-positive (HER2+) early-stage and metastatic breast cancers. However, diarrhea has been reported as a common adverse event leading to neratinib discontinuation. Results from the CONTROL trial suggest that proactive diarrhea management with antidiarrheal prophylaxis or dose escalation of neratinib from a lower starting dose to the full FDA-approved dose of 240 mg/day can reduce the incidence, duration, and severity of neratinib-associated diarrhea in patients with early-stage breast cancer. Dose escalation has been included in the FDA-approved label for both early-stage and metastatic HER2+ breast cancer since June 2021. CASE SERIES: This series of five cases details real-world clinical implementation of strategies for management of neratinib-induced diarrhea in patients with early-stage and metastatic HER2+ breast cancer, including a patient with a pre-existing gastrointestinal disorder. MANAGEMENT AND OUTCOME: In four of five cases, diarrhea was managed with neratinib dose escalation, and antidiarrheal prophylaxis with loperamide plus colestipol was used in the remaining case. Management of diarrhea allowed all patients to remain on therapy. DISCUSSION: This case series shows that neratinib-associated diarrhea can be managed effectively with neratinib dose escalation from a lower initial starting dose and/or prophylactic antidiarrheal medications in a real-world clinical setting. The findings highlight the importance of patient-provider communication in proactive management of adverse events. Widespread implementation of the strategies described here may improve adherence and thereby clinical outcomes for patients with HER2+ breast cancer treated with neratinib.

Survivorship, Version 1.2021.

The NCCN Guidelines for Survivorship are intended to help healthcare professionals working with cancer survivors to ensure that each survivor's complex and varied needs are addressed. The Guidelines provide screening, evaluation, and treatment recommendations for consequences of adult-onset cancer and its treatment; recommendations to help promote healthful lifestyle behaviors, weight management, and immunizations in survivors; and a framework for care coordination. This article summarizes the recommendations regarding employment and return to work for cancer survivors that were added in the 2021 version of the NCCN Guidelines.

Reducing time to treatment and patient costs with breast cancer: the impact of patient visits.

BACKGROUND: The purpose of this study was to evaluate the impact of processes aimed at reducing time to treatment initiation (TTI) on minimizing the days spent to complete pretreatment visits and the associated costs for patients with nonmetastatic breast cancer. METHODS: System-wide initiatives were implemented in 2014 to minimize TTI, by incorporating multiple strategies (eg, creation of teams, patient liaisons, process mapping) and enhanced communication to increase coordinated visits. Average number of days spent to complete visits, TTI, and associated patient costs including driving expenses, parking, food, childcare, and lost wages were calculated and compared between the years 2015 and 2018. RESULTS: In 2015, the median TTI was 43.5 days and the average number of separate days spent to attend multidisciplinary visits prior to first treatment was 1.86. These were reduced to 29 days and 1.52 visits, respectively, in 2018 (p < 0.0001 for both). When evaluating treatment visits by surgical procedure, the average number of visits was reduced regardless of surgical procedure. The average number of visits was highest for patients undergoing mastectomy with reconstruction (2.34 in 2015, reduced to 1.65 in 2018, p < 0.0001). A single visit to complete treatment planning was associated with patient costs of $249 as compared with multiple trips costing $491 for 2 visits and up to $1,226 for 5 visits. CONCLUSIONS: In breast cancer patients, implementing processes to reduce time to treatment was associated with fewer visits required prior to treatment initiation, resulting in lower patient costs.

IMPROVE, a community-based exercise intervention versus support group to improve functional and health outcomes among older African American and Non-Hispanic White breast cancer survivors from diverse socioeconomic backgrounds: Recruitment strategies and baseline characteristics.

BACKGROUND: Behavioral intervention studies in older breast cancer survivors, particularly older African American (AA) and socioeconomic status-disadvantaged breast cancer survivors, are lacking. To inform future studies, the authors examined recruitment strategies in older breast cancer survivors who participated in an exercise intervention study. METHODS: IMPROVE is a randomized trial designed to evaluate a group-based exercise intervention versus a support group (ClinicalTrials.gov identifier, NCT02763228). Participants were aged ≥65 years who had survived stage I through III breast cancer and were within 5 years of treatment completion. Participants were recruited through multiple approaches, including peripheral, linguistic, and constituent-involving strategies that incorporated the identification of potentially eligible patients from 3 local hospitals and from State of Ohio registries and through direct clinician and community organization referrals. RESULTS: Between October 2016 and November 2019, 7487 patients were screened, 4790 were potentially eligible, and 213 were randomized into the study. The eligible:randomization rates were 4.4% overall and 84%, 8%, and 2% for recruitment using direct referrals, hospital registries, and state registries, respectively. The median age of the randomized cohort was 70 years (range, 65-88 years) and included 44% AA and 44% socioeconomic status-disadvantaged breast cancer survivors. Compared with all registry-eligible patients, directly referred-eligible patients were more likely to be AA versus Non-Hispanic White (41% vs 19%; P = .006), to be contacted successfully (100% vs 33%; P < .0001), and to accept study participation (88% vs 16%; P < .0001). CONCLUSIONS: Direct referrals appeared to be the most efficient strategy for recruiting AA survivors. Behavioral intervention studies seeking to target older AA and socioeconomic status-disadvantaged breast cancer survivors should include strategies that foster direct referrals to study participation.

Physical Activity Before, During, and After Chemotherapy for High-Risk Breast Cancer: Relationships With Survival.

BACKGROUND: Although physical activity has been consistently associated with reduced breast cancer mortality, evidence is largely based on data collected at one occasion. We examined how pre- and postdiagnosis physical activity was associated with survival outcomes in high-risk breast cancer patients. METHODS: Included were 1340 patients enrolled in the Diet, Exercise, Lifestyle and Cancer Prognosis (DELCaP) Study, a prospective study of lifestyle and prognosis ancillary to a SWOG clinical trial (S0221). Activity before diagnosis, during treatment, and at 1- and 2-year intervals after enrollment was collected. Patients were categorized according to the Physical Activity Guidelines for Americans as meeting the minimum guidelines (yes/no) and incrementally as inactive, low active, moderately active (meeting the guidelines), or high active. RESULTS: In joint-exposure analyses, patients meeting the guidelines before and 1 year after diagnosis experienced statistically significant reductions in hazards of recurrence (hazard ratio [HR] = 0.59, 95% confidence interval [CI] = 0.42 to 0.82) and mortality (HR = 0.51, 95% CI = 0.34-0.77); associations were stronger at 2-year follow-up for recurrence (HR = 0.45, 95% CI = 0.31 to 0.65) and mortality (HR = 0.32, 95% CI = 0.19 to 0.52). In time-dependent analyses, factoring in activity from all time points, we observed striking associations with mortality for low- (HR = 0.41, 95% CI = 0.24 to 0.68), moderate- (HR = 0.42, 95% CI = 0.23 to 0.76), and high-active patients (HR = 0.31, 95% CI = 0.18 to 0.53). CONCLUSIONS: Meeting the minimum guidelines for physical activity both before diagnosis and after treatment appears to be associated with statistically significantly reduced hazards of recurrence and mortality among breast cancer patients. When considering activity from all time points, including during treatment, lower volumes of regular activity were associated with similar overall survival advantages as meeting and exceeding the guidelines.

Real-world Outcomes of Cyclin-dependent Kinase Inhibitors Continued Beyond First Disease Progression in Hormone Receptor-positive Metastatic Breast Cancer.

BACKGROUND: CDK4/6 inhibitors (CDK4/6i), in combination with aromatase inhibitors, are United States Food and Drug Administration-approved for the treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). The effectiveness of continuing them beyond first disease progression (PD) is currently unknown. This retrospective study evaluated the impact of the continuation of CDK4/6i beyond first PD in HR+/HER2- MBC using real-world experience. PATIENTS AND METHODS: A single-institution retrospective review of patients with HR+ MBC who received CDK4/6is from 2015 to 2018 and where CDK4/6is were continued beyond first PD. The primary outcome was progression-free survival (PFS) after initial PD on CDK4/6i therapy. RESULTS: Thirty women with HR+/HER2- MBC met eligibility criteria. Patients were identified from a prospective database of patients at the Cleveland Clinic Foundation who were prescribed CDK4/6is. The median age and follow-up duration were 47.5 years and 27 months, respectively. Most patients received palbociclib (PA)/letrozole as initial therapy (67%), followed by PA/fulvestrant (23%), and PA/other aromatase inhibitor (20%), and abemaciclib with either fulvestrant or letrozole (6%). As of January 31, 2019, 25 (83.3%) patients were still alive, and 19 (63%) patients had progressed. The estimated median PFS for continued CDK4/6i use beyond the first PD was 11.8 months (95% confidence interval, 5.34-13.13 months). CONCLUSIONS: Among a small cohort of patients with HR+ MBC in a non-clinical trial setting, continuation of CDK4/6i-endocrine treatment post initial PD was associated with a median PFS of about 12 months. Formal randomized clinical trials evaluating the continuation of CDK4/6is beyond the first PD are currently ongoing and will provide more answers to this important clinical question.