e23111 Background: Acupuncture has been shown to reduce aromatase inhibitor-induced arthralgias, as well as possibly hot flashes and fatigue, but research has been limited. The purpose of this study was to evaluate real world perceived benefit of acupuncture for commonly experienced symptoms among breast cancer survivors. Methods: Breast cancer survivors who had used acupuncture for cancer- or treatment-related symptoms were identified using an ongoing prospective Mayo Clinic Breast Disease Registry (MCBDR) cohort. In addition, Mayo Clinic electronic health records (EHR) were queried to identify additional participants. All identified patients were mailed a survey with acupuncture-related questions. Respondents were also asked to recall their severity of arthralgia, myalgia, post-surgical pain, hot flashes, nausea/vomiting, fatigue, depression, anxiety, insomnia, lymphedema, headache, and neuropathy from 1 to 5 (1 = mild, 5 = severe) before and after acupuncture treatment. Results: Acupuncture use was reported among 413 participants in MCBDR (12% of all enrollees) and 73 patients were identified in the Mayo EHR. 241 eligible women returned surveys (median age at diagnosis 50 yrs). Mean symptom severity scores decreased from before to after acupuncture by at least 1 point for all queried symptoms (Table). Conclusions: Acupuncture is frequently used by patients for a variety of breast cancer-related symptoms. Those who do pursue acupuncture usually perceive few toxicities and substantial benefits. Cost may be a barrier to treatment for some. [Table: see text]
Ondansetron versus palonosetron as a marker of non-adherence to antiemetic prophylaxis guidelines in highly emetogenic chemotherapy.
e23108 Background: ASCO antiemetic guidelines recommend upfront triple prophylaxis (NK1 receptor antagonist (RA) + 5HT3 RA + dexamethasone) for patients receiving highly emetogenic chemotherapy (HEC). Physicians exhibit high variation in HEC guideline adherence, principally involving inclusion of NK1 RA. Whether adherence is associated with selection of the specific 5HT3 RA agent remains inadequately studied. Methods: In the IBM Explorys electronic health record database, we used procedure and diagnosis codes to identify HEC courses and related nausea/vomiting (NV) from 2012 to 2018. We defined HEC guideline adherence as triple prophylaxis at chemotherapy initiation. We assigned HEC courses for ≥ 7 day cycles of cisplatin or anthracycline + cyclophosphamide (AC), or carboplatin (≥ 14 day cycles as a proxy for AUC ≥ 4) to prescribing oncologists based on encounter frequency. We categorized 5HT3 RA use of each physician treating ≥ 5 HEC courses based on their most commonly used 5HT3 and performed descriptive statistics. Results: Of 12,262 HEC courses, 57% involved physicians having greater use of ondansetron (OND) (mean OND to palonosetron (PALO) ratio of 3.9:1). These courses had lower guideline adherence (due to NK1 RA omission) and higher rates of NV for combined HEC, AC, and carboplatin. NV rates for cisplatin did not vary by 5HT3 agent used. Courses involving physicians with greater PALO use (mean OND:PALO ratio of 0.2:1) had superior adherence and NV rates, despite involving a slightly higher risk population (younger and/or female). Conclusions: According to HEC antiemetic guidelines, NK1 RA use should occur independent of 5HT3 RA agent selection. However, we observed less NK1 RA use where OND was preferred, which may have caused the observed higher rates of NV with OND. Further evaluation should assess whether pharmacy cost minimization is a driver of both OND preference and NK1 omission in HEC. [Table: see text]
Long-term neurotoxicity in women with breast cancer.
e23089 Background: Taxanes (paclitaxel and docetaxel) are commonly administered as part of chemotherapy for breast cancer, but long-term data on chemotherapy-induced peripheral neuropathy (CIPN) are limited in this population. We aimed to assess CIPN approximately three years after an initial exposure to paclitaxel or docetaxel. Methods: In a cross-sectional observation study, which surveyed consented enrollees annually after receipt of care at Mayo Clinic for a new breast cancer diagnosis over age 18, we collected patient-reported EORTC CIPN20 data by mailed questionnaire at baseline and three years after a breast cancer diagnosis. We then confirmed patient-reported chemotherapy data by chart abstraction and only included those who had received a standard course of docetaxel-based or paclitaxel-based chemotherapy, but had not had other neurotoxic treatment for cancer. CIPN20 overall and sensory scale raw scores were converted to a 0-100 linear scale with lower scores indicating more severe symptoms. Results: 84 women who received a taxane for breast cancer completed the survey. 82 were treated in the adjuvant or neo-adjuvant setting, while 2 received a taxane for metastatic breast cancer. 67 women received paclitaxel, while 17 received docetaxel. The median age at diagnosis was 51.5 years (range 31-86). 37 had estrogen receptor (ER) and/or progesterone receptor (PR) positive and human epidermal growth factor receptor-2 (Her2) negative, 31 Her2 positive, and 16 triple negative breast cancer. The median CIPN20 score was 92.98 (range 33.33-100). The median sensory CIPN score was 92.59 (range 25.94-100). 81% of women had an overall CIPN20 score of less than 100, and 68% had a sensory score of less than 100. Conclusions: The majority of women who received a taxane based chemotherapy regimen for breast cancer reported at least mild neuropathic symptoms three years out from treatment. Additional research is needed to help tailor chemotherapy decisions to toxicity risks and to reduce the likelihood of long-term CIPN, which can impair quality of life.
Systematic review and meta-analysis of definitions and reported incidences of anthracycline cardiotoxicity.
e23081 Background: Anthracycline-induced cardiotoxicity (AIC) is a well-known phenomenon, but the true incidence is poorly defined, and definitions of AIC in the literature are variable. We performed a systematic review and meta-analysis to elucidate AIC definitions and the incidence of clinical heart failure (HF) and subclinical AIC reported in adult breast cancer and lymphoma patients after anthracycline (AC) therapy. Methods: 3,428 abstract and titles were identified via PubMed search. Inclusion criteria for full text review included minimum of 100 adult patients receiving ACs; median/mean follow up of at least 12 months; and specified evaluation of left ventricular ejection fraction. Outcomes were divided into clinical HF and subclinical AIC. Meta-analysis was performed with MedCalc software with random effects model. Results: 366 full text articles were reviewed. 24 studies, including a total of 11,065 patients, reported clinical HF findings; 21 studies, including a total of 8,098 patients, reported subclinical AIC findings. Meta-analysis showed an overall incidence of clinical HF of 3.1% (range 0 to 29%, CI 1.9 to 4.6%, I2= 93.9%); an incidence of 2.0% (CI 0.9 to 3.6%, I2 = 91.6%) in breast cancer patients receiving AC; and 4.8% in lymphoma patients receiving AC (CI 2.1 to 8.6%, I2 = 93.6%). Subclinical AIC was seen in 13.8% overall patients (range 2 to 45%, CI 10.4 to 17.7%, I2= 95.3%); 10.3% of breast cancer patients (CI 7.0 to 14.3%, I2= 95.0%); and 19.8% of lymphoma patients (CI 12.3 to 28.6%, I2= 94.4%). Incidence of HF correlated with increasing age (r = 0.51, p = 0.06) and cumulative dose (r = 0.51 , p = 0.19). There was notable heterogeneity of AIC definitions between studies (Table). Conclusions: Cardiotoxicity is not uncommon among patients who receive AC, particularly at doses given for the treatment of lymphoma. However, there was considerable heterogeneity in HF incidences. More uniform criteria and precise estimates are needed to inform clinical practice and trials. [Table: see text]
Diagnostic and treatment delays in young women with breast cancer.
6575 Background: Delays in diagnosis (dx) and treatment (tx) affect breast cancer (BC) outcomes. We sought to identify factors associated with delays among young women, who do not undergo routine screening and often have pregnancy or breastfeeding-related breast changes that may mask a BC. Methods: The Young Women’s Breast Cancer Study is a multicenter, prospective cohort that enrolled 1302 women with newly dx BC age ≤40 between 2006-2016. Women reported the method and timing of cancer detection on the baseline survey. 231 were ineligible or excluded due to missing information. Among those reporting self-detected cancers, using multivariable regression we evaluated factors associated with delays ≥90 days (d) from symptom to presentation (self delay) and presentation to dx (care delay); in stage 0-III BC we evaluated delays ≥60d from dx to tx (tx delay). Results: 1071 eligible women had median age at dx of 37 yrs (17-40) and 74% reported self-detected cancers. Self delay or care delay ≥90d was reported in 17% and 13%, respectively. Factors inversely associated with self delay included pregnancy at dx (vs nulliparous, OR 0.10, CI 0.01-0.78) and perceived financial comfort (vs not, OR 0.62, CI 0.41-0.93). Women dx ≤1 year post-partum who breastfed (vs nulliparous, OR 2.60, CI 1.14-5.93) and those with a family history of breast/ovarian cancer (vs none, OR 1.79, CI 1.00-3.19) were more likely to have a care delay. Age was inversely associated with care delays (OR 0.94, CI 0.89-0.99). Tx delay was reported by 10% (105/1015), and associated with being single (vs partnered, OR 1.61, CI 1.02-2.56 ), non-white (vs white, OR 1.85, CI 1.09-3.13) and having Stage 0 BC (vs stage 1, OR: 3.08, CI 1.65-5.77); women with stage 3 BC (vs stage 1, OR 0.13, CI 0.03-0.56) were less likely to have a tx delay. Conclusions: In this cohort, most young women with BC underwent timely dx and tx initiation. Women dx ≤1 year post-partum who breastfed were more likely to experience a care delay, likely because lactational changes may mask BC signs and symptoms. The associations of perceived financial status with self delay and non-white race with tx delay underscore the need for additional support to ensure timely care for underserved populations with the goal of eliminating disparities in outcomes.
Previsit breast cancer educational microlearning videos: Impact on patient satisfaction and engagement.
6526 Background: Most patients diagnosed with breast cancer turn to the Internet to learn about their diagnosis; however, information online is often generic, challenging to navigate, and not expert-curated. To facilitate patient education and engagement in our breast clinic, we piloted the implementation of pre-visit education via brief microlearning videos organized within an online platform. Methods: Seventeen videos of 2-4 minute duration were developed by multidisciplinary content experts. Videos covered a variety of educational topics relevant to breast cancer, including treatment options. Patients received a link via email to create an account, which provided access to the platform. Aggregate viewing data and optional patient surveys (online after viewing 3 videos and at the clinical appointment) were used to assess opt-in rates, engagement, and satisfaction. Results: Between September 2018 and January 2019, 57.4% (240/418) of women with biopsy proven breast cancer who were sent an email invitation registered on the platform. On average, patients watched 11 of the 17 videos, with 93.7% of users (225/240) viewing at least one. Overall, 85% (168/198) of women recommend the microlearning format for patient education. The most-viewed video topics included types of breast cancer, breast abnormality and biopsy, understanding biopsy results, tumor markers, and staging. Seventy-eight percent (154/198) of women reported that they planned to share the videos with family or caregivers, and 67% (133/198) felt that the educational content increased their satisfaction with their overall experience. Barriers to video access were emails marked as junk, not having an email address, and difficulties with videos loading. Conclusions: The majority of patients participating in this pilot registered on the platform and watched pre-visit microlearning educational videos. These expert-curated videos contributed to high levels of satisfaction and engagement. Strategies to overcome barriers to access will be developed to expand the reach of this new valuable component of breast cancer care.
Genomics of HER2+ breast cancer in young women before and after exposure to chemotherapy (chemo) plus trastuzumab (H).
554 Background: HER2+ breast cancer (BC) is particularly common in young women. Genomic features of HER2+ tumors before and after H-based therapy have not been described in a population of young women and may point to clinically targetable mechanisms of resistance. Methods: From a large prospective cohort of women diagnosed with BC age ≤40 years, we identified those with HER2+ BC and tumor tissue available for sequencing before and after chemo+H. Whole exome sequencing (WES) was performed on each tumor and on germline DNA from blood. Tumor-normal pairs were analyzed for mutations and copy number (CN) changes. Evolutionary analysis was performed for patients with both pre- and post-treatment (tx) samples. Results: 22 women had successful WES samples from at least one timepoint; 13 of these had paired sequencing results both before and after chemo+H. For the majority of women, post-tx sample was following neoadjuvant chemo + H, though post-tx timepoint for other women represented locoregional or distant metastasis (Table). TP53 was the only gene that was significantly recurrently mutated in both pre- and post-tx samples. Comparison of matched pre-tx and post-tx samples demonstrated that large changes in HER2 CN over the course of tx were uncommon, only 2/13 pts had > 2-fold change in HER2 CN. Other clonal and subclonal genomic alterations were found to be acquired in the post-tx sample compared to the pre-tx sample. One patient acquired a putative activating mutation in ERBB2. Another patient acquired a clonal hotpsot mutation in TP53. MYC gene amplification was observed in 4 post-tx tumors. NOTCH2 alterations were found in post-tx biopsies from 2 different patients, and mutations in STIL were also found in post-tx biopsies from 2 patients, though the function of these mutations is not known. Conclusions: HER2+ breast tumors in young women display genomic evolution following tx with chemo+H. HER2 CN changes are uncommon, but we identified several genes that warrant exploration as potential mechanisms of resistance to therapy in this population.[Table: see text]
Nonadherent behaviors among young women on adjuvant endocrine therapy for breast cancer
Background Young age is a known factor associated with suboptimal adherence to endocrine therapy (ET) for adjuvant breast cancer (BC) treatment. This study was aimed at assessing nonadherent behaviors and associated factors among young women with early‐stage hormone receptor–positive BC. Methods As part of a multicenter, prospective cohort of women with a diagnosis of BC at or under the age of 40 years, participants were surveyed 30 months after their diagnosis about adherent behaviors. Among those who reported taking ET, adherence was measured with a 3‐item Likert‐type scale: Do you ever forget to take your ET? If you feel worse when you take your ET, do you stop taking it? Did you take your ET exactly as directed by your doctor over the last 3 months? Women reporting at least 1 nonadherent behavior were classified as nonadherers. Variables with a P value <.20 were included in a multivariable logistic model. Results Among 384 women, 194 (51%) were classified as nonadherers. Univariate factors that retained significance in the multivariable model included educational level (odds ratio [OR], 0.50 for high vs low; P = .04), level of social support according to the Medical Outcome Study Social Support Survey (OR, 0.98 per 1 point; P = .01), and confidence with the decision regarding ET measured on a 0 to 10 numerical scale (OR, 0.63 for high vs low; P = .04). Conclusions Findings from this study could help to identify young patients at higher risk for nonadherence. Interventions adapted to the level of education and aimed at reinforcing support and patients' confidence in their decision to take ET could improve adherence and associated outcomes in this population.
Abstract GS6-06: Local therapy and quality of life outcomes in young women with breast cancer
Abstract Background: Increasing rates of mastectomy, primarily bilateral mastectomy (BMx), have been most dramatic in young women with breast cancer (BC). Impact on long-term quality of life (QOL) is largely unknown. Methods: Between 10/2016-11/2017, we administered the BREAST-Q, a validated patient-reported outcomes measure, to women dx with BC at age ≤40 in a large prospective cohort study. Demographic and treatment information was obtained by surveys and chart review. Mean BREAST-Q scores for each domain (breast satisfaction, physical, psychosocial, and sexual) were compared by surgery types; higher BREAST-Q scores (range: 0-100) indicate better QOL. Linear regression was used to identify predictors of BREAST-Q domain scores. Results: 581 women with stage 0-3 BC completed the BREAST-Q a median of 5.8 years from dx. Median age at dx was 37 (range: 26-40) years; 86% had stage 0, 1 or 2 disease; 28% had breast-conserving surgery (BCS); 72% had mastectomy (Mx), among whom 72% underwent BMx and 89% had reconstruction. Mean BREAST-Q scores (unadjusted) for breast satisfaction, psychosocial, and sexual well-being were lower for patients having unilateral mastectomy (UMx) or BMx compared to BCS; physical function was similar among groups. In multivariate analysis, lower BREAST-Q psychosocial scores were associated with radiation and Mx (UMx or BMx). Lower sexual well-being scores were also associated with Mx. Lower satisfaction with breast scores following radiation were of a clinically significant magnitude (β -8.1 95% CI -11.9- -4.3, p-value 0.03). Lower scores for physical well-being were seen for patients reporting lymphedema and higher for those who had undergone surgery more than 5 years prior. Lower scores across all 4 domains were associated with reported financial distress. BREAST-Q domain mean scores (SD) BMxUMxBCSp-valueBreast satisfaction60.3 (18.9)59.5 (21.3)65.9 (20.7)0.008Physical well-being78.6 (14.9)79.7 (15.1)78.9 (15.5)0.8Psychosocial well-being68.1 (20.8)70.5 (21.2)76.1 (20.5)<0.001Sexual well-being48.6 (21.3)53.2 (21.7)57.5 (18.7)<0.001SD Standard deviation Conclusion: Local therapy in young breast cancer survivors may have a persistent impact on their breast satisfaction, psychosocial, and sexual outcomes, with particular effects from UMx or BMx. Socio-economic stressors also appear to play a role. When counseling young women about their surgical decisions, knowledge of potential long-term QOL impact is of critical importance. Citation Format: Dominici LS, Hu J, King TA, Ruddy KJ, Tamimi RM, Peppercorn J, Schapira L, Borges VF, Come SE, Warner E, Partridge AH, Rosenberg SM. Local therapy and quality of life outcomes in young women with breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS6-06.
Abstract GS6-01: Surgical treatment after neoadjuvant systemic therapy in young women with breast cancer: Results from a prospective cohort study
Abstract Background Young women are more likely than older women to present with higher stage breast cancer (BC) and may benefit to a greater extent from downstaging with neoadjuvant systemic treatment (NST). Young age is also associated with greater likelihood of pathologic complete response (pCR). Using a large prospective cohort of young women with BC, we investigated response to neoadjuvant therapy, eligibility for breast conserving surgery (BCS) pre- and post-NST, and surgical treatment. Methods The Young Women's Breast Cancer Study (YWS) is a multi-center cohort of women diagnosed with BC at age ≤40, that enrolled 1302 patients from 2006 to 2016. Disease characteristics and treatment information were obtained through medical record and central pathology review. Surgical recommendation before and after NST, conversion from BCS borderline/ineligible to BCS eligible, surgery, documented reasons for choosing mastectomy (MTX) among BCS eligible women, and final pathologic response were independently reviewed. Results Among 1302 women enrolled in YWS, 801 (62%) presented with unilateral stage I-III breast cancer and 317(40%) received NST. Median age was 36 years old (22-40). Pre-NST, 85/317 (27%) were BCS eligible, 49 (15%) were borderline, and 169 (53%) were not eligible (16 inflammatory breast cancer (IBC), 88 large tumor size /cosmetic, 48 diffuse calcifications, and 83 multicentricity). Among the 218 patients who were BCS ineligible/borderline pre-NST, 82 (38%) became eligible for BCS after NST. 4 patients who were BCS eligible pre-NST became ineligible. Of all patients eligible for BCS post-NST (n=163), 80 (49%) attempted BCS, 74 (93%) of whom were successful, and 83 (51%) chose MTX. Reasons for choosing MTX included: patient preference (38/83 (46%)), BRCA or TP53 mutation (31 (37%)), family history (3 (4%)), unknown (11 (13%)). On final pathology, 75 (24%) patients had pCR. Among patients who achieved a pCR, 48 (64%) underwent MTX, fewer than half (21/48 (44%)) were for anatomic indications (IBC, large tumor at diagnosis, diffuse calcifications, multicentric disease). Conclusion While NST doubled the proportion of young women eligible for BCS, nearly half chose MTX regardless of response to NST, mostly for personal preference or high-risk preventative reasons. These data highlight that surgical decision making among young women with breast cancer is often driven by factors beyond extent of disease and clinical response to therapy. Table 1.Clinical-pathologic characteristicsCharacteristicsNumber%Pre NST surgical recommendation BCS eligible8526.8Borderline4915.5BCS ineligible16953.3Unknown144.4Clinical Response Complete20263.7Partial9229.0Stable30.9Progressing72.2Unknown134.1Pathologic Response pCR (No invasive or DCIS)7524No pCR24276Post NST Surgical recommendation BCS eligible16351.4BCS ineligible14445.4Unknown103.2Attempted surgery BCS8025.2MTX23674.1Unknown20.6Final Surgery BCS7423.3MTX24176unknown20.6 Citation Format: Kim HJ, Dominici L, Rosenberg S, Pak LM, Poorvu PD, Ruddy K, Tamimi R, Schapira L, Come S, Peppercorn J, Borges V, Warner E, Vardeh H, Collins L, King T, Partridge A. Surgical treatment after neoadjuvant systemic therapy in young women with breast cancer: Results from a prospective cohort study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS6-01.