Psychosocial and supportive care concerns of young women living with advanced breast cancer: baseline findings from a prospective virtual support intervention study.

PURPOSE: Adolescent and young adults (AYAs) with metastatic breast cancer (MBC) experience high physical and psychosocial burdens compounded by a disrupted life trajectory. We sought to determine the psychosocial and supportive care concerns of this population to better understand and address unmet needs. METHODS: AYAs diagnosed with MBC (18-39 years) participating in a prospective interventional study (Young, Empowered, and Strong) at Dana-Farber Cancer Institute completed an electronic survey following enrollment. Measures evaluated sociodemographics, health behaviors, quality of life, and symptoms, among others. We used two-sided Fisher's exact tests to determine associations between concerns (e.g., cancer progression, side effects, lifestyle, finances, fertility) and demographic variables. RESULTS: Among 77 participants enrolled from 9/2020-12/2022, average age at MBC diagnosis and survey was 35.9 (range: 22-39) and 38.3 years (range: 27-46), respectively. Most were non-Hispanic white (83.8%) and 40.3% reported their diagnosis caused some financial problems. Many were concerned about fertility (27.0%), long-term treatment side effects (67.6%), exercise (61.6%), and diet (54.1%). Select concerns varied significantly by age, race/ethnicity, and education. Younger women at survey reported greater concern about familial cancer risk (p = 0.028). Women from minority racial/ethnic groups more frequently reported issues talking about their cancer to family/friends (p = 0.040) while those with more education were more frequently concerned with long-term effects of cancer on their health (p = 0.021). CONCLUSION: Young women living with MBC frequently report psychosocial, health, and cancer management concerns. Tailoring supportive care and communications to address prevalent concerns including disease progression and treatment side effects may optimize wellbeing.

Taxanes for the treatment of breast cancer during pregnancy: an international cohort study.

INTRODUCTION: The addition of taxanes to anthracycline-based chemotherapy is considered standard of care in the treatment of breast cancer. However, there are insufficient data regarding the safety of taxanes during pregnancy. The aim of this study was to describe the incidence of obstetric and neonatal adverse events associated with the use of taxane-containing chemotherapy regimens for the treatment of breast cancer during pregnancy. METHODS: This is a multicenter, international cohort study of breast cancer patients treated with taxanes during pregnancy. A descriptive analysis was undertaken to synthetize available data. RESULTS: A total of 103 patients were included, most of whom were treated with paclitaxel and anthracyclines given in sequence during gestation (90.1%). The median gestational age at taxane initiation was 28 weeks (range = 12-37 weeks). Grade 3-4 adverse events were reported in 7 of 103 (6.8%) patients. The most common reported obstetric complications were intrauterine growth restriction (n = 8 of 94, 8.5%) and preterm premature rupture of membranes (n = 5 of 94, 5.3%). The live birth rate was 92 of 94 (97.9%), and the median gestational age at delivery was 37 weeks (range = 32-40 weeks). Admission to an intensive care unit was reported in 14 of 88 (15.9%) neonates, and 17 of 70 (24.3%) live births resulted in small for gestational age neonates. Congenital malformations were reported in 2 of 93 (2.2%). CONCLUSION: Obstetric and neonatal outcomes after taxane exposure during pregnancy were generally favorable and did not seem to differ from those reported in the literature with standard anthracycline-based regimens. This study supports the use of taxanes during gestation when clinically indicated.

Conception and pregnancy among women with a live birth after breast cancer treatment: A survey study of young breast cancer survivors.

BACKGROUND: Breast cancer (BC) is the most common malignancy in women of reproductive age. This study sought to explore the postcancer conception and pregnancy experience of young BC survivors to inform counseling. METHODS: In the Young Women's Breast Cancer Study (NCT01468246), a multicenter, prospective cohort, participants diagnosed at age ≤40 years with stage 0-III BC who reported ≥1 postdiagnosis live birth were sent an investigator-developed survey. RESULTS: Of 119 eligible women, 94 (79%) completed the survey. Median age at diagnosis was 32 years (range, 17-40) and at first postdiagnosis delivery was 38 years (range, 29-47). Most had stage I or II (77%) and HR+ (78%) BC; 51% were nulligravida at diagnosis. After BC treatment, most (62%) conceived naturally, though 38% used assisted reproductive technology, 74% of whom first attempted natural conception for a median of 9 months (range, 2-48). Among women with a known inherited pathogenic variant (n = 20), two underwent preimplantation genetic testing. Of 59 women on endocrine therapy before pregnancy, 26% did not resume treatment. Hypertensive disorders of pregnancy (20%) was the most common obstetrical condition. Nine percent of newborns required neonatal intensive care unit admission and 9% had low birth weight. CONCLUSION: Among women with live births after BC treatment, most conceived naturally and having a history of BC did not appear to negatively impact pregnancy complications, though the high rate of hypertensive disorders of pregnancy warrants further investigation. The prolonged period of attempting natural conception for some survivors suggests the potential need for improved understanding and counseling surrounding family planning goals after BC.

Survivorship Navigation for Young Women With Early-Stage Breast Cancer.

BACKGROUND: Young women treated for breast cancer experience unique concerns in follow-up. We developed a program to direct young breast cancer survivors to a dedicated survivorship visit and evaluated their experience. MATERIALS AND METHODS: Early-stage breast cancer patients diagnosed under age 45 within 1 year of completing breast surgery, chemotherapy and/or radiation therapy were systematically referred for a survivorship visit. Patients completed a one-time, post-visit survey about their experience. RESULTS: Sixty-nine out of 89 (78%) eligible patients attended a survivorship visit, and 40 of those 69 (58%) completed the post-visit survey. Most respondents learned about the survivorship clinic after completing treatment (30/40; 75%) and reported the survivorship visit occurred at an appropriate time in their follow-up care (26/40; 65%). Of the 34 respondents who reported receiving a treatment summary and survivorship care plan, 30 indicated it would be helpful when visiting their primary care provider (88.2%). Participants reported gaining valuable knowledge about cancer treatment (28/38; 73.7%), side effects (32/39; 82.1%), and cancer surveillance (30/40; 75%), and discussed emotional health (32/40; 80%), exercise (38/40; 95%), and ongoing cancer surveillance (32/37; 86.5%). Several reported intentions to make changes to their follow-up oncology care (8/20; 40%), exercise routines (16/30; 53.3%), and emotional health care (15/22; 68.2%). DISCUSSION: Survivorship visit navigation is feasible for young breast cancer patients. These visits can influence knowledge gained and intended future health plans and behaviors. Systematic approaches to survivorship care may improve the physical and mental health of cancer survivors. Future health care delivery research focused on survivorship is warranted.

Endocrine Therapy Synergizes with SMAC Mimetics to Potentiate Antigen Presentation and Tumor Regression in Hormone Receptor-Positive Breast Cancer.

Immunotherapies have yet to demonstrate significant efficacy in the treatment of hormone receptor-positive (HR+) breast cancer. Given that endocrine therapy (ET) is the primary approach for treating HR+ breast cancer, we investigated the effects of ET on the tumor immune microenvironment (TME) in HR+ breast cancer. Spatial proteomics of primary HR+ breast cancer samples obtained at baseline and after ET from patients enrolled in a neoadjuvant clinical trial (NCT02764541) indicated that ET upregulated ß2-microglobulin and influenced the TME in a manner that promotes enhanced immunogenicity. To gain a deeper understanding of the underlying mechanisms, the intrinsic effects of ET on cancer cells were explored, which revealed that ET plays a crucial role in facilitating the chromatin binding of RelA, a key component of the NF-κB complex. Consequently, heightened NF-κB signaling enhanced the response to interferon-gamma, leading to the upregulation of ß2-microglobulin and other antigen presentation-related genes. Further, modulation of NF-κB signaling using a SMAC mimetic in conjunction with ET augmented T-cell migration and enhanced MHC-I-specific T-cell-mediated cytotoxicity. Remarkably, the combination of ET and SMAC mimetics, which also blocks prosurvival effects of NF-κB signaling through the degradation of inhibitors of apoptosis proteins, elicited tumor regression through cell autonomous mechanisms, providing additional support for their combined use in HR+ breast cancer. SIGNIFICANCE: Adding SMAC mimetics to endocrine therapy enhances tumor regression in a cell autonomous manner while increasing tumor immunogenicity, indicating that this combination could be an effective treatment for HR+ patients with breast cancer.

Extended adjuvant endocrine therapy in a longitudinal cohort of young breast cancer survivors.

Extended adjuvant endocrine therapy (eET) improves outcomes in breast cancer survivors. Most studies however have been limited to postmenopausal women, and optimal eET for young survivors is uncertain. We report eET use among participants in the Young Women's Breast Cancer Study (YWS), a multicenter prospective cohort of women age ≤40 newly diagnosed with breast cancer enrolled between 2006-2016. Women with stage I-III hormone receptor-positive breast cancer, ≥6 years from diagnosis without recurrence were considered eET candidates. Use of eET was elicited from annual surveys sent years 6-8 after diagnosis, censoring for recurrence/death. 663 women were identified as eET candidates with 73.9% (490/663) having surveys eligible for analysis. Among eligible participants, mean age was 35.5 (±3.9), 85.9% were non-Hispanic white, and 59.6% reported eET use. Tamoxifen monotherapy was the most reported eET (77.4%), followed by aromatase inhibitor (AI) monotherapy (21.9%), AI-ovarian function suppression (AI-OFS) (6.8%) and tamoxifen-OFS (3.1%). In multivariable analysis, increasing age (per year odds ratio [OR]: 1.10, 95% confidence interval [CI]: 1.04-1.16), stage (II v. I: OR: 2.86, 95% CI: 1.81-4.51; III v. I: OR: 3.73, 95%CI: 1.87-7.44) and receipt of chemotherapy (OR: 3.66, 95% CI: 2.16-6.21) were significantly associated with eET use. Many young breast cancer survivors receive eET despite limited data regarding utility in this population. While some factors associated with eET use reflect appropriate risk-based care, potential sociodemographic disparities in uptake warrants further investigation in more diverse populations.

Effects of an educational physical activity intervention in young women with newly diagnosed breast cancer: Findings from the Young and Strong Study.

BACKGROUND: Obesity and inactivity are poor prognostic factors in breast cancer, but less is known regarding physical activity (PA) and weight patterns in young breast cancer survivors. METHODS: The Young and Strong Study was a cluster-randomized trial evaluating education and support interventions for young women (age <45 years) with newly diagnosed breast cancer. Sites were randomized 1:1 to a Young Women's Intervention (YWI) or a contact-time control physical activity intervention (PAI). Changes in PA and weight were compared between groups using general estimating equations to evaluate clustered binary and Gaussian data. RESULTS: A total of 467 patients enrolled between July 2012 and December 2013 across 54 sites. Median age at diagnosis was 40 years (range, 22-45). At baseline, median body mass index (BMI) was 25.4 kg/m2 (range, 16.1-61.1), and participants reported a median of 0 minutes (range, 0-2190) of moderate/vigorous PA/week. PA increased significantly over time in both groups (p < .001), with no difference between groups at any time point. BMI increased modestly but significantly (p < .001) over time in both groups. Provider attention to PA was observed in 74% of participants on PAI and 61% on YWI (p = .145) and correlated with PA at 12 months (median 100 min/week of PA in participants with provider attention to PA vs. 60 min/week in those without, p = .016). CONCLUSIONS: In a cohort of young women with breast cancer, rates of obesity and inactivity were high. PA and BMI increased over time and were not impacted by an educational PA intervention. Findings provide important information for developing lifestyle interventions for young breast cancer survivors.

Clonal Hematopoiesis in Young Women Treated for Breast Cancer.

PURPOSE: Young women treated for breast cancer with cytotoxic therapies are at risk for clonal hematopoiesis of indeterminate potential (CHIP), a condition in which blood cells carrying a somatic mutation associated with hematologic malignancy comprise at least 4% of the total blood system. CHIP has primarily been studied in older patient cohorts with limited clinical phenotyping. EXPERIMENTAL DESIGN: We performed targeted sequencing on longitudinal blood samples to characterize the clonal hematopoietic landscape of 878 women treated for breast cancer enrolled in the prospective Young Women's Breast Cancer Study. RESULTS: We identified somatic driver mutations in 252 study subjects (28.7%), but only 24 (2.7%) had clones large enough to meet criteria for CHIP. The most commonly mutated genes were DNMT3A and TET2, similar to mutations observed in noncancer cohorts. At 9-year median follow-up, we found no association between the presence of a somatic blood mutation (regardless of clone size) and adverse breast cancer (distant relapse-free survival) or non-breast cancer-related outcomes in this cohort. A subset of paired blood samples obtained over 4 years showed no evidence of mutant clonal expansion, regardless of genotype. Finally, we identified a subset of patients with likely germline mutations in genes known to contribute to inherited cancer risk, such as TP53 and ATM. CONCLUSIONS: Our data show that for young women with early-stage breast cancer, CHIP is uncommon after cytotoxic exposure, is unlikely to contribute to adverse outcomes over the decade-long follow-up and may not require additional monitoring if discovered incidentally.

Adjuvant endocrine therapy non-initiation and non-persistence in young women with early-stage breast cancer.

PURPOSE: Characterizing oral adjuvant endocrine therapy (ET) non-initiation and non-persistence in young women with breast cancer can inform strategies to improve overall adherence in this population. METHODS: We identified 693 women with hormone receptor-positive, stage I-III breast cancer enrolled in a cohort of women diagnosed with breast cancer at age ≤ 40 years. Women were classified as non-initiators if they did not report taking ET in the 18 months after diagnosis. Women who initiated but did not report taking ET subsequently (through 5-year post-diagnosis) were categorized as non-persistent. We assessed ET decision-making and used logistic regression to identify factors associated with non-initiation/non-persistence and to evaluate the association between non-persistence and recurrence. RESULTS: By 18 months, 9% had not initiated ET. Black women had higher odds and women with a college degree had lower odds of non-initiation. Among 607 women who initiated, 20% were non-persistent. Younger age, being married/partnered, and reporting more weight problems were associated with higher odds of non-persistence; receipt of chemotherapy and greater hot flash and vaginal symptom burden were associated with lower odds of non-persistence. Adjusting for age and clinical characteristics, non-persistence was associated with lower odds of recurrence. Women who initiated were more likely to report shared decision-making than non-initiators (57% vs. 38%, p = 0.049), while women who were non-persistent were less likely to indicate high confidence with the decision than women who were persistent (40% vs. 63%, p < 0.001). CONCLUSION: Interventions to improve ET decision-making may facilitate initiation and address barriers to adherence in young breast cancer survivors. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , NCT01468246.

Treatment discontinuation, patient-reported toxicities and quality-of-life by age following trastuzumab emtansine or paclitaxel/trastuzumab (ATEMPT).

In the ATEMPT trial, adjuvant trastuzumab emtansine (T-DM1) compared to paclitaxel plus trastuzumab (TH) for stage I HER2-positive breast cancer improved patient-reported outcomes (PROs), while maintaining excellent disease outcomes. We report treatment discontinuation and use multivariable models to compare, patient-reported toxicity and quality-of-life (QOL) by age (≤50, >50) and treatment arm at 18 months post-enrollment among 366 eligible participants randomized in a 3:1 ratio to T-DM1 or TH. T-DM1 discontinuation was higher among women >50 vs. ≤50 (23% vs. 9%, p = 0.003, Fisher's Exact test) with 4%, 8%, and 17% of older patients discontinuing treatment by 3, 6, and 9 months, respectively. Superior QOL with T-DM1 vs. TH was observed among women ≤50 with estimated mean difference of 6.48 (95% confidence interval (CI) 0.51-12.46) and driven by better social/family well-being and breast cancer-specific sub-scores. Among women >50, T-DM1 was associated with superior physical well-being and less activity impairment, with no differences in global QOL. Older women had decreased neuropathy with T-DM1 vs. TH. De-escalated treatment regimens for HER2 positive breast cancer may have age-varying impact on treatment tolerance, toxicities and subsequent QOL, which should be considered when selecting therapy options.Clinical Trial Registration: ClinicalTrials.gov, NCT01853748.

Patient perspectives on testing for clonal hematopoiesis of indeterminate potential.

Clonal hematopoiesis of indeterminate potential (CHIP), an emerging biomarker for personalized risk-directed interventions, is increased in cancer survivors. However, little is known about patient preferences for CHIP testing. We surveyed participants in a prospective cohort study of young women with breast cancer (BC). The emailed survey included an introduction to CHIP and a vignette eliciting participants' preferences for CHIP testing, considering sequentially: population-based 10-year risk of BC recurrence, hematologic malignancy, and heart disease; increased CHIP-associated risks; current CHIP management; dedicated CHIP clinic; and hypothetical CHIP treatment. Preference changes were evaluated using the McNemar test. The survey response rate was 82.2% (528/642). Median age at time of survey was 46 years and median time from diagnosis was 108 months. Only 5.9% had prior knowledge of CHIP. After vignette presentation, most survivors (87.1%) recommended CHIP testing for the vignette patient. Presented next with CHIP-independent, population-based risks, 11.1% shifted their preference from testing to not testing. After receiving information about CHIP-associated risks, an additional 10.1% shifted their preference to testing. Preference for testing increased if vignette patient was offered a CHIP clinic or hypothetical CHIP treatment, with 7.2% and 14.1% switching preferences toward testing, respectively. Finally, 75.8% of participants desired CHIP testing for themselves. Among participants, 28.2% reported that learning about CHIP caused at least moderate anxiety. Most young survivors favored CHIP testing, with preferences influenced by risk presentation and potential management strategies. Our findings highlight the importance of risk communication and psychosocial support when considering biomarkers for future risk in cancer survivors. This trial has been registered at www.clinicaltrials.gov as #NCT01468246.

Body weight changes and associated predictors in a prospective cohort of young breast cancer survivors.

BACKGROUND: Weight gain after a breast cancer diagnosis is common and is associated with inferior outcomes. Young survivors may be especially susceptible to weight changes given the impact of treatment on menopausal status. METHODS: The authors identified women who were diagnosed with stage 0 to III breast cancer at age 40 years or younger between 2006 and 2016 from a multicenter prospective cohort. Self-reported weight was collected at diagnosis and at 1 year and 3 years postdiagnosis. Tumor and treatment data were obtained from medical records and patient surveys. Multinomial logistic regression was used to identify the factors associated with weight gain (≥5%) or weight loss (≥5%) versus stable weight at 1 year and 3 years postdiagnosis. RESULTS: The cohort included 956 women with a median age of 37 years at diagnosis. Mean weight significantly increased over time from 66.54 ± 14.85 kg at baseline to 67.33 ± 15.53 and 67.77 ± 14.65 kg at 1 year and 3 years, respectively (p ≤ .001 for both comparisons). The proportion of women experiencing ≥5% weight gain increased from 24.8% at 1 year to 33.9% at 3 years. At 1 year, less self-perceived financial comfort, Black race, and stage III disease were significantly associated with weight gain; at 3 years, only less self-perceived financial comfort remained significant. Baseline overweight or obesity was significantly associated with weight loss at both time points. Chemotherapy, endocrine therapy, and treatment-related menopause were not associated with weight change. CONCLUSIONS: One third of young breast cancer survivors experienced clinically significant weight gain 3 years after diagnosis; however, treatment-related associations were not observed. Age-appropriate lifestyle interventions, including the reduction of financial barriers, are needed to prevent weight gain in this high-risk population.

The prevalence and predictors of adjuvant chemotherapy use among patients treated with neoadjuvant endocrine therapy.

PURPOSE: Neoadjuvant endocrine therapy (NET) facilitates clinical response and breast conservation in hormone receptor-positive (HR-positive) breast cancer. Patient selection for adjuvant chemotherapy (CT) post-NET is unclear and potentially evolving with use of genomic assays. We evaluated post-NET CT use in a national dataset. METHODS: Using the National Cancer DataBase, we identified patients with cT2-3N0-3M0 HR-positive/human epidermal growth factor receptor 2-negative breast cancer treated between 2010 and 2017 with 3-12 months of NET prior to breast surgery. CT use was evaluated in the overall population, in patients with a pathologic complete response (pCR) and in patients with ypT1-2N0 disease (approximating PEPI 0). Exploratory analysis included patients > 50 years with ypN0-1, and 21-gene recurrence score (RS) ≤ 25 (approximating TAILORx/RxPONDER populations not benefiting from CT). Multivariable logistic regression was used to identify factors associated with CT. RESULTS: Among 3624 eligible patients, 20.4% (740/3624) received CT. On multivariable analysis, age ≤ 50, lobular histology, grade 2, progesterone receptor negativity, ypT3, ypN + and RS ≥ 18 were associated with CT receipt. Co-morbidity, longer NET duration, ypT4, ypNx, and RS < 18 were associated with CT omission. CT was administered to 3.3% (1/30) of patients experiencing pCR and 5.5% (82/1483) with ypT1-2N0 disease. Among patients > 50 years with ypT0-3N0-1 residual disease, 13.8% (355/2569) received CT; RS was available for 24.8% (88/355) and 60% (53/88) had a score 0-25. CONCLUSION: A minority of patients receive CT post-NET. This decision appears to be driven by younger age, RS and pathological nodal status. Increased consideration of these factors prior to neoadjuvant treatment choice may be warranted.

Outcomes after treatment of breast cancer during pregnancy including taxanes and/or granulocyte colony-stimulating factor use: findings from a multi-institutional retrospective analysis.

BACKGROUND: Guidelines support comparable treatment for women diagnosed with breast cancer during pregnancy (PrBC) and nonpregnant women with limited case-specific modifications to ensure maternal-fetal safety. Experience during pregnancy with modern agents, such as taxanes or granulocyte colony-stimulating factors (GCSF), is limited. PATIENTS AND METHODS: We retrospectively identified a multi-institutional cohort of PrBC between 1996 and 2020. Propensity score analyses with multiple imputation for missing variables were applied to determine the associations between chemotherapy exposures during pregnancy, with or without taxanes or GCSF, and a compound maternal-fetal outcome including spontaneous preterm birth, preterm premature rupture of membranes, chorioamnionitis, small for gestational age newborns, congenital malformation, or 5-min Apgar score < 7. RESULTS: Among 139 PrBC pregnancies, 82 (59.0%) were exposed to chemotherapy, including 26 (31.7%) to taxane and 18 (22.0%) to GCSF. Chemotherapy use, in general, and inclusion of taxane and/or GCSF, specifically, increased over time. Pregnancies resulting in live singleton births (n = 123) and exposed to chemotherapy were as likely to reach term as those that were not (59.5% vs. 63.6%, respectively, punadjusted = 0.85). Among women treated with chemotherapy, propensity score-matched odds ratios (OR) for the composite maternal-fetal outcome were not significantly increased with taxane (OR 1.24, 95% CI 0.27-5.72) or GCSF (OR 2.11, 95% confidence interval (CI) 0.48-9.22) with similar effects in multiple imputation and sensitivity models. CONCLUSION: The judicious increased use of taxane chemotherapy and/or growth factor support during pregnancy was not associated with unfavorable short-term maternal-fetal outcomes. While these findings are reassuring, case numbers remain limited and continued surveillance of these patients and progeny is warranted.

Optimal Endocrine Therapy in Premenopausal Women: A Pragmatic Approach to Unanswered Questions.

Recent epidemiologic data show an increasing incidence of breast cancer among premenopausal women in many higher-income countries. Among premenopausal women, those diagnosed under age 40 years experience inferior long-term outcomes, particularly in the setting of hormone receptor-positive, human epidermal growth factor receptor 2-negative disease. In addition to more advanced disease presentation and/or less favorable disease biology, suboptimal adjuvant endocrine therapy (ET) has emerged as an important driver of this age-related disparity. Historically, young women have been excluded from treatment with aromatase inhibitors (AIs), attained low rates of chemotherapy-related amenorrhea, and exhibited low adherence to ET. Recently, several studies have demonstrated treatment with ovarian function suppression (OFS) during the first 5 years postdiagnosis to be associated with improvements in breast cancer recurrence and mortality, with additional benefits achieved from pairing OFS with an AI. As the first 5 years of ET for premenopausal women has been transformed, extended ET, administered in years 5-10 postdiagnosis, has also become more common. However, the only studies of extending ET in premenopausal women have tested an additional 5 years of tamoxifen following an initial 5 years of tamoxifen and studies of AIs in the second 5 years have been limited to postmenopausal women. Herein, we review available data concerning potential benefits and risks to be considered when counseling premenopausal women on extended ET, including the continuation of OFS. We offer a pragmatic framework to support decision making given the current body of knowledge and call out the need for additional research into this issue.

Young, Empowered and Strong: A Web-Based Education and Supportive Care Intervention for Young Women With Breast Cancer Across the Care Continuum.

PURPOSE: Patient-centered digital interventions may help empower young women to self-manage symptoms and psychosocial concerns and support informational needs often unaddressed in clinic. METHODS: Young, Empowered and Strong (YES) is an interactive web-based intervention designed to engage young women with personalized education and symptom self-management resources on the basis of responses to patient-reported outcome-based questionnaires. We piloted YES among young women (< 45 years) with newly diagnosed early breast cancer (EBC) or metastatic breast cancer (MBC) and breast cancer survivors (BCSs). Assessments were deployed weekly (EBC and MBC) or every 4 weeks (BCSs) over 12 weeks. At study completion, use, feasibility, and acceptability of YES were evaluated via a survey and semistructured interview. RESULTS: Thirty women were enrolled between April and June 2019: 10 EBC, 10 BCSs, and 10 MBC. The mean age at diagnosis and enrollment was 36 (range 25-44) and 39 (range 31-44) years, respectively. Most participants were actively treated (96%, 27 of 28) with endocrine therapy (54%, 15 of 28) or chemotherapy (43%, 12 of 28). Overall, 61% (180 of 296) of assessments were completed (EBC: 70%, BCSs: 63%, and MBC: 52%). Of 37 patient-reported outcome and need domains, the most frequently triggered were sexual health (EBC: 90%, BCSs: 90%, and MBC: 90%), anxiety (EBC: 80%, BCSs: 90%, and MBC: 90%), stress and mindfulness (EBC: 80%, BCSs: 90%, and MBC: 90%), and fatigue (EBC: 90%, BCSs: 80%, and MBC: 90%). On postpilot survey, participants reported that YES helped them to learn (50%, 7 of 14), monitor (43%, 6 of 14), and manage (57%, 8 of 14) their symptoms. CONCLUSION: YES is a feasible and acceptable digital intervention to support young women across the breast cancer care continuum. The nearly universal triggering of sexual and mental health needs suggests suboptimal management in the clinical setting and the potential for self-management through a digital platform.

Neoadjuvant Endocrine Therapy in Clinical Practice: A Review.

IMPORTANCE: In clinical practice, neoadjuvant endocrine therapy (NET) is rarely used despite being an effective treatment modality able to downstage tumors and facilitate breast-conserving surgery. OBSERVATIONS: Using data from studies conducted since 2000, we provide readers with a critical in-depth review on clinical aspects related to the application of NET in the treatment of hormone receptor (HR)-positive/ERBB2 (formerly HER2)-negative breast cancer. This includes an overview of patient-selection criteria, regimen choice, treatment duration, evaluation of response by imaging, interpretation of pathology after treatment, and surgical considerations. Areas of controversy include the use of gene-expression tests for patient selection, treatment of premenopausal women, surgical management of the axilla after NET, and adjuvant systemic therapy decision-making, including the use of chemotherapy. CONCLUSIONS AND RELEVANCE: NET is an optimal treatment modality for a considerable proportion of postmenopausal women diagnosed with HR-positive tumors. The treatment landscape for HR-positive breast cancer is evolving, with novel agents and the growing use of gene expression profiling to define treatment selection. As such, it is likely that NET use will increase and the practical considerations outlined here will become more important.

Prognostic Utility of Breast Cancer Index to Stratify Distant Recurrence Risk in Invasive Lobular Carcinoma.

PURPOSE: The prognostic utility of Breast Cancer Index (BCI) for risk assessment of overall (0-10 years), early (0-5 years), and late (5-10 years) distant recurrence (DR) in hormone receptor-positive (HR+) invasive lobular carcinoma (ILC) was evaluated. EXPERIMENTAL DESIGN: BCI gene expression analysis was performed blinded to clinical outcome utilizing tumor specimens from patients with HR+ ILC from a multi-institutional cohort. The primary endpoint was time to DR. Kaplan-Meier analyses of overall, early, and late DR risk were performed, and statistical significance was evaluated by log-rank test and Cox proportional hazards regression. The prognostic contribution of BCI in addition to clinicopathologic factors was evaluated by likelihood ratio analysis. RESULTS: Analysis of 307 patients (99% ER+, 53% T1, 42% N+, 70% grade II) showed significant differences in DR over 10 years based on BCI risk categories. BCI low- and intermediate-risk patients demonstrated similar DR rates of 7.6% and 8.0%, respectively, compared with 27.0% for BCI high-risk patients. BCI was a significant independent prognostic factor for overall 10-year DR [HR = 4.09; 95% confidence interval (CI), 2.00-8.34; P = 0.0001] as well as for both early (HR = 8.19; 95% CI, 1.85-36.30; P = 0.0042) and late (HR = 3.04; 95% CI, 1.32-7.00; P = 0.0224) DR. In multivariate analysis, BCI remained the only statistically significant prognostic factor for DR (HR = 3.49; 95% CI, 1.28-9.54; P = 0.0150). CONCLUSIONS: BCI is an independent prognostic factor for ILC and significantly stratified patients for cumulative risk of 10-year, early, and late DR. BCI added prognostic value beyond clinicopathologic characteristics in this distinct subtype of breast cancer.

Chemotherapy-related amenorrhea (CRA) after adjuvant ado-trastuzumab emtansine (T-DM1) compared to paclitaxel in combination with trastuzumab (TH) (TBCRC033: ATEMPT Trial).

PURPOSE: Chemotherapy-related amenorrhea (CRA) is a surrogate for ovarian toxicity and associated risk of infertility and premature menopause. Here, we compare CRA rate with paclitaxel (T)-trastuzumab (H) to that with ado-trastuzumab emtansine (T-DM1). METHODS: Patients with T1N0 HER2 + early-stage breast cancer (eBC) enrolled on the ATEMPT trial and were randomized 3:1 to T-DM1 3.6 mg/kg IV every (q) 3 weeks (w) × 17 vs. T 80 mg/m2 with H IV qw × 12 (4 mg/kg load → 2 mg/kg), followed by H (6 mg/kg IV q3w × 13). Enrollees who self-reported as premenopausal were asked to complete menstrual surveys at baseline and every 6-12 months for 60 months. 18-month CRA (no periods reported during prior 6 months on 18-month survey) was the primary endpoint of this analysis. RESULTS: Of 512 ATEMPT enrollees, 123 who began protocol therapy and answered baseline and at least one follow-up menstrual survey were premenopausal at enrollment. 76 had menstrual data available at 18 months without having received a gonadotropin-releasing hormone agonist or undergone hysterectomy and/or oophorectomy. Median age was 45 (range 23-53) among 18 who had received TH and 46 (range 34-54) among 58 who had received T-DM1. The 18-month rate of CRA was 50% after TH and 24% after T-DM1 (p = 0.045). CONCLUSION: Amenorrhea at 18 months was less likely in recipients of adjuvant T-DM1 than TH. Future studies are needed to understand how T-DM1 impacts risk of infertility and permanent menopause, and to assess amenorrhea rates when T-DM1 is administered after standard HER2-directed chemotherapy regimens.

Impact of fertility concerns on endocrine therapy decisions in young breast cancer survivors.

BACKGROUND: The diagnosis and treatment of breast cancer can have profound effects on a young woman's family planning and fertility, particularly among women with hormone receptor-positive breast cancer. METHODS: The Young Women's Breast Cancer Study was a multicenter cohort of women aged 40 years or younger and newly diagnosed with breast cancer from 2006 to 2016. Surveys included assessments of fertility concerns, endocrine therapy (ET) preferences, and use. Characteristics were compared between women who reported that fertility concerns affected ET decisions and those who did not. Logistic regression was used to identify factors associated with having an ET decision affected by fertility concerns. RESULTS: Of 643 eligible women with hormone receptor-positive, stage I to III breast cancer, one-third (213 of 643) indicated that fertility concerns affected ET decisions. In a multivariable analysis, only parity at diagnosis was significantly associated with fertility concerns affecting ET decisions (odds ratio for nulliparous vs ≥2 children, 6.96; 95% confidence interval, 4.09-11.83; odds ratio for 1 vs ≥2 children, 5.30; 95% confidence interval, 3.03-9.87). Noninitiation/nonpersistence was higher among women with fertility concerns versus those without fertility concerns (40% vs 20%; P < .0001). Among women with fertility-related ET concerns, 7% (15 of 213) did not initiate ET, and 33% (70 of 213) were nonpersistent over 5 years of follow-up. Of these women, 66% (56 of 85) reported 1 or more pregnancies or pregnancy attempts; 27% (15 of 56) had resumed ET at the last available follow-up through 5 years. CONCLUSIONS: Concern about fertility is a contributor to adjuvant ET decisions among a substantial proportion of young breast cancer survivors. Ensuring family planning is addressed in the setting of ET recommendations should be a priority throughout the cancer care continuum.