Received Hormone Therapy Research Articles

Cancer Registry Data Linkage of Electronic Health Record Data From ASCO's CancerLinQ: Evaluation of Advantages, Limitations, and Lessons Learned.

To evaluate the completeness of information for research and quality assessment through a linkage between cancer registry data and electronic health record (EHR) data refined by ASCO's health technology platform CancerLinQ. A probabilistic data linkage between Iowa Cancer Registry (ICR) and an Iowa oncology clinic through CancerLinQ data was conducted for cases diagnosed between 2009 and 2018. Demographic, cancer, and treatment variables were compared between data sources for the same patients, all of whom were diagnosed with one primary cancer. Treatment data and compliance with quality measures were compared among those with breast or prostate cancer; SEER-Medicare data served as a comparison. Variables captured only in CancerLinQ data (smoking, pain, and height/weight) were evaluated for completeness. There were 6,175 patients whose data were linked between ICR and CancerLinQ data sets. Of those, 4,291 (70%) were diagnosed with one primary cancer and were included in analyses. Demographic variables were comparable between data sets. Proportions of people receiving hormone therapy (30% v 26%, P < .0001) or immunotherapy (22% v 12%, P < .0001) were significantly higher in CancerLinQ data compared with ICR data. ICR data contained more complete TNM stage, human epidermal growth factor receptor 2 testing, and Gleason score information. Compliance with quality measures was generally highest in SEER-Medicare data followed by the combined ICR-CancerLinQ data. CancerLinQ data contained smoking, pain, and height/weight information within one month of diagnosis for 88%, 52%, and 76% of patients, respectively. Linking CancerLinQ EHR data with cancer registry data led to more complete data for each source respectively, as registry data provides definitive diagnosis and more complete stage information and laboratory results, whereas EHR data provide more detailed treatment data and additional variables not captured by registries.

Synchronous and metachronous bilateral breast cancer among women with a history of lobular carcinoma in situ.

Lobular carcinoma in situ (LCIS) confers increased cancer risk in either breast, but it remains unclear if this population is at increased risk for bilateral breast cancer (BC) development. Here we report bilateral BC incidence among women with a history of LCIS. Women with classic-type LCIS diagnosed from 1980 to 2017 who developed unilateral BC (UBC) or bilateral BC were identified. Bilateral BC was categorized as synchronous (bilateral BC diagnosed < 6months apart; SBBC) or metachronous (bilateral BC diagnosed ≥ 6months apart; MBBC). Five-year incidence rates of bilateral BC among this population were evaluated. Comparisons were made to identify factors associated with bilateral BC. At 7years' median follow-up, 249/1651 (15%) women with LCIS developed BC; 34 with bilateral BC (2%). There were no clinicopathologic feature differences between those with UBC and bilateral BC. SBBC occurred in 18 without significant differences versus UBC. Among 211 with UBC and a contralateral breast at risk, 16 developed MBBC at a median follow-up of 3years. MBBC patients were less likely to receive endocrine therapy and more likely to receive chemotherapy versus UBC. Tumor histology was not associated with MBBC. Estimated 5-year MBBC risk was 6.4%. Index estrogen/progesterone receptor positivity and endocrine therapy were the only factors associated with MBBC risk. Bilateral BC occurred in 2% of women with LCIS history at median follow-up of 7years. Similar to the general BC population, a decrease in MBBC is seen among women with a history of LCIS who develop hormone receptor-positive disease and those who receive endocrine therapy, highlighting the protective effects of this treatment.

Analysis of adverse event of interstitial lung disease in men with prostate cancer receiving hormone therapy using the Food and Drug Administration Adverse Event Reporting System.

To investigate interstitial lung disease (ILD) in men with prostate cancer receiving hormone therapy. We gathered cases diagnosed with prostate cancer based on the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database from 2004 to 2020. We divided the included cases into 3 groups based on the primary suspected drugs: a hormone therapy group, a positive control group (taxanes), and a negative control group. We employed reporting odds ratio, a disproportionality method, to detect the association between ILD events and target drugs. We finally included a total of 85 403 cases, 69 894 cases (628 ILD event cases) in the hormone therapy group, 2302 cases (158 ILD event cases) in the positive control group and 13 207 cases (72 ILD event cases) in the negative control group. There were 394 ILD event cases (62.74%) in the hormone therapy group in Japan; 78.68% of the ILD events occurred within the first year after hormone treatment. Disproportionality analysis indicated that ILD events were significantly associated with nilutamide, flutamide, bicalutamide, goserelin, degarelix and apalutamide; the reporting odds ratios (95% confidence interval) were 32.14 (11.03-93.63), 9.93 (3.62-27.21), 8.19 (6.01-11.16), 3.74 (2.61-5.37), 2.41 (1.55-3.75) and 1.94 (1.01-3.75), respectively. Based on this FAERS pharmacovigilance analysis, the association between ILD events and hormone therapy drugs, including bicalutamide, flutamide, nilutamide, goserelin, degarelix and apalutamide, should not be ignored, especially in the Japanese population. Lung function of prostate cancer patients should be monitored when receiving the hormone therapy drugs mentioned above, especially for the first year post medication.

Effectiveness and Safety of Palbociclib plus Endocrine Therapy in Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: Real-World Results.

Real-world data are critical to demonstrate the reproducibility of evidence and the external generalizability of randomized clinical trials. Palbociclib is an oral small-molecule inhibitor of cyclin-dependent kinases 4/6 that has been shown to improve progression-free survival when combined with letrozole or fulvestrant in phase 3 clinical trials. To evaluate real-world outcomes in patients with metastatic breast cancer who received palbociclib in combination with endocrine therapy in routine clinical practice. In this retrospective observational multicentre study, data were evaluated for all women with metastatic breast cancer who were treated with palbociclib from April 2017 to September 2019. Treatment response was assessed through progression-free survival according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Fifty-three patients were included in the study, with median age 57 years (range 31-87 years). For all patients treated with palbociclib, median progression-free survival by the end of the study period was 14.4 months (95% confidence interval [CI] 6.2-22.2 months). Twenty-three women who received palbociclib as a first-line treatment did not experience progression-free survival; for these patients, the median treatment duration was 12.1 months (95% CI 1.4-28.0 months). For the 23 patients who received palbociclib as second-line therapy for metastatic breast cancer, median progression-free survival was 13.3 months (95% CI 4.1-22.4 months). Among the 7 women who received palbociclib as third-line therapy, median progression-free survival was 6.0 months (95% CI 0.9-11.1 months). The most common adverse events were hematologic, with grade 3 or 4 neutropenia occurring in 20 (38%) of the 53 patients. This study provides data from a real-world setting that match the results of previous studies in terms of effectiveness (i.e., progression-free survival) when palbociclib plus endocrine therapy was used as second- or third-line treatment. Palbociclib had appropriate tolerability and a profile of easily manageable adverse effects, with none of the patients suspending their treatment because of toxic effects.

Older patients' experience of living with cognitive impairment related to hormone therapy for breast cancer: A qualitative study.

Patients with breast cancer may develop cognitive impairment as a result of hormone therapy and aging. This study aimed to describe older patients' experience of cognitive impairment related to hormone therapy for breast cancer. A qualitative and descriptive design was used. Semi-structured interviews were conducted with 11 patients asking about their experience in daily life related to their cognitive impairment. Study participants were evaluated by cancer-specific geriatric assessment. Inductive content analysis was conducted using the interview records. Three themes emerged from the patients' narrative data: recognizing of cognitive impairments, impacts on mental health, and coping with cognitive impairments. Recognizing of cognitive function consisted of two categories: perception of cognitive changes and acknowledging their cognitive function status through interacting with others. Impacts on mental health consisted of six categories: decreased motivation for social activities, upset by perception of cognitive decline, concerns about impacts of cognitive impairment on treatment of breast cancer, concerns about the care burden of their family, concerns about progression of cognitive impairments, and feeling secure that their cognitive impairment is not unusual. Coping with cognitive impairments consisted of two categories: coping with problems related to cognitive impairment and trying to maintain and improve cognitive function. Oncology nurses should assess cognitive function and complete a comprehensive evaluation of older patients receiving hormone therapy for breast cancer. An evaluation of cognitive function would enable a tailored approach to education and support to enhance coping ability in the longer term.

Prostate Cancer Disparities in Hispanics Using the National Cancer Database

ObjectivesTo evaluate the differences in prostate cancer characteristics and treatment between Hispanic Americans with different countries of origin using the National Cancer Database. MethodsWe performed a retrospective analysis of 54,947 adult Hispanic Americans diagnosed with prostate cancer between 2004 and 2015. Origin was Mexican (N = 7844; 14.3%), South/Central American (N = 4010; 7.3%), Puerto Rican (N = 2938; 5.4%), Cuban (N = 2549; 4.6%), Dominican (N = 1535; 2.8%), Hispanic not specified (N = 36,269; 65.7%). Comparison between characteristics among Hispanic American sub-groups’ categories was performed using chi-square and Kruskal-Wallis tests for categorical and continuous variables respectively. ResultsMexicans had overall worse disease at presentation including highest median PSA (7.8 ng/mL), most prevalent T3/T4 stage (6.7%), M1 stage (8.9%), and high-grade Gleason scores (24.0%) when compared to all other Hispanic American groups. Cubans were most likely to receive hormone therapy and radiation therapy and least likely to receive surgical treatment. Compared to Mexicans, Cubans (hazards ratio [HR] = 1.30, 95% confidence interval = [1.16-1.44]) had worse overall survival, while Puerto Ricans (HR = 1.08 [0.95-1.19] had similar overall survival, and Dominicans (HR = 0.63 [0 0.53-0.75]), South/Central Americans (HR = 0.75, [0.66-0.84]) and not specified (HR = 0.84 [0.79-0.91]) had better survival. ConclusionAmong Hispanic Americans with different countries of origin, disparities in prostate cancer characteristics, treatment choice, and survival do exist. Mexicans had the least favorable prostate cancer characteristics at presentation. Cubans had the worst overall survival while they were also most likely to receive hormone and/or radiation as first-line treatment. Our analysis demonstrates significant heterogeneity in the Hispanic American population.

Effectiveness of Sildenafil in Erectile Sexual Dysfunction in Prostate Cancer Patients

Introduction: Prostate cancer is the first cause of death by cancer in Cuban men and affects the quality of their sexual life. Objective: To investigate the efficacy of sildenafil in the treatment of erectile dysfunction in patients with prostate cancer after hormone or radiotherapy. Method: An observational, double perspective and cross-sectional study was conducted in the Service of Urology of Hospital “Dr. Agostinho Neto” in Guantanamo from 2014 to 2018, which was approved by the medical ethics committee. The study consisted of 70 patients diagnosed with prostate cancer who received hormone therapy or radiotherapy with erectile dysfunction. In each patient, we studied age, cancer treatment, time of postoperative dysfunction, and the response of penile erectile function to the use of sildenafil. Results: 37.2% of the patients were between 70 and 79 years old, and 79.1% of the patients received hormone therapy; the highest proportion of erectile dysfunction occurred 1–2 years after treatment (48.8%); 81.4% responded adequately to sildenafil treatment, which was not related to hormone or radiotherapy for cancer. Conclusions: Prostate cancer patients treated with hormone and/or radiotherapy benefit from the efficacy of sildenafil.

Energy expenditure profiles and the risk of early limiting toxicity in older patients with cancer: The ELCAPA-25 prospective cohort survey

Predicting the risk of early limiting toxicity (ELT) is major challenge for the clinician seeking an effective, safe treatment for older patients with cancer. The Cancer and Aging Research Group (CARG) and CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients) toxicity scores were designed to predict chemotherapy-related toxicity. Elevated resting energy expenditure (REE) may predispose to cachexia and increase ELT and mortality in older patients with cancer. The primary objective was to assess the association between elevated REE and ELT in older patients with cancer. The secondary objectives were to assess the discriminant ability of a predictive model including REE (relative to the CARG and CRASH scores) and the prognostic value of elevated REE. We assessed patients aged 70 or over included in the prospective ELCAPA cohort between 2014 and 2018. The inclusion criteria were a solid tumour, a measurement of REE at baseline (mREE, by indirect calorimetry), and a geriatric assessment prior to cancer treatment in a teaching hospital (Paris, France). The mREE was compared with the predicted REE (pREE), as defined by the Harris-Benedict equation. Depending on the mREE/pREE ratio, study participants were classified as hypermetabolic, hypometabolic or normometabolic. The primary endpoint was 3-month ELT, defined as any unplanned hospitalization or any event leading to dose reduction, a treatment delay of more than 7 days, or treatment discontinuation within 3 months of initiation. The secondary endpoint was the 3-month mortality rate. A total of 179 patients were included. The median age was 80 [interquartile range: 76-84] years, 37% of the patients were female, 81.8% had metastatic disease, 67.6% received chemotherapy, 20.7% received hormone therapy, and 11.7% received targeted therapies. According to the mREE/pREE ratio, 85 patients (47%) were hypermetabolic, 63 (35%) were normometabolic, and 31 (18%) were hypometabolic. Sixty patients (33.5%; 95% confidence interval (CI): 26.7-40.9) experienced ELT. The discriminant ability (as assessed by the C-index) of a multivariate model including REE and adjustment factors was 0.82 [95%CI: 0.73-0.91]. In comparison, the discriminant ability of the CARG and CRASH models was 0.57 [0.45-0.68] and 0.51 [0.40-0.62], respectively. In our model, hypermetabolism was an independent risk factor for ELT (adjusted odds ratio=2.44; 95%CI: 1.02-5.80). Other risk factors were the cancer type and stage, the treatment protocol, a clinical diagnosis of depression, the presence of grade 3 or 4 comorbidities, and the serum lactate dehydrogenase level. Hypermetabolism status is an independent predictor of ELT in older patients with cancer, relative to normometabolic status. Baseline REE measurement might improve the ELT risk assessment and decision-making process.

Abstract P2-08-16: The cross-talk between nuclear p-ser294-FOXO3a and cytoplasmic MMP-2 in breast cancer survival and treatment response

Abstract Background The forkhead protein FOXO3a, the member of the forkhead box O (FOXO) transcription factors, controls a wide spectrum of carcinogenesis, therapy response and progression in human cancer. Emerging evidence suggest that phosphorylation of FOXO3a by ERK and p38 at Serine 294 induces its nuclear localization or exclusion to the cytosol, therefore regulating FOXO3a transcriptional activity and consequently promoting cell proliferation and tumorigenesis. Several proteins regulated by FOXO3a, such as MMP-2,9 and 13, are involved in metastasis. We aim to explore the potential role of p-ser294-FOXO3a and MMPs, and interplay between both in breast cancer. Materials and Methods Paraffin-embedded tissue microarrays from 350 breast cancer patients were enrolled. Immunohistochemical analysis was performed, and the expression patterns of p-ser294-FOXO3a, MMP-2, MMP-9, MMP-13 were categorized by semiquantitative method and further correlated with the clinicopathological parameters using the x2 test. Survival curves were calculated using the Kaplan-Meier method, while the significance was determined by log rank test. The biological impacts and underlying mechanisms of p-ser294-FOXO3a were analyzed by transwell assay, RT-PCR, western blotting immunofluorescence staining. co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP) assay in breast cancer cells upon transfection with FOXO3a and FOXO3a mutant (S294A). Results Our results showed that nuclear p-Ser294-FOXO3a index was inversely correlated with tumor grade (p=0.011) and relapse (p=0.053), but positively correlated only with cytoplasmic MMP-2 intensity (p=0.010). It is noted that cytoplasmic MMP-2 intensity was positively correlated with tumor grade (p=0.032) and size (p=0.028). Intriguingly, decreased nuclear p-Ser294-FOXO3a index was significantly associated with an improved overall survival rate (p=0.004) and of those patients bearing high MMP-2 staining (p&amp;lt;0.001) or negative ER status (p=0.006), and those receiving hormone therapy (HT) (p=0.030) or chemotherapy (p=0.001). Ectopic FOXO3a overexpression increased invasion rate which was inhibited by tamoxifen (TAM) in only ER-positive MCF-7 cells. In addition, TAM inhibited the invasion rates of ERα-negative MDA-MB-231 cells when co-expressed FOXO3a and ERα, and Ser294Ala-FOXO3a mutant (S294A) is incompetent for TAM-mediated suppression of invasion. Real time qPCR showed that TAM decreased FOXO3a-induced MMP-2 mRNA expression in MCF-7 cells and in MDA-MB-231 cells co-expressed with ERα. Co-immunoprecipitation and immunofluorescent staining showed that Ser294 phosphorylation of FOXO3a might be essential for its nuclear localization and protein-protein interaction with ERα in response to TAM. Conclusion The present study highlights that the real index of nuclear p-ser294-FOXO3a can predict a better survival rate and treatment response of HT and chemotherapy in breast cancer. Furthermore, the specific interplay among p-ser294-FOXO3a, ERα, and MMP-2 might be involved in breast cancer metastasis and treatment response. A better understanding of the underlying mechanism may improve the treatment strategy of specific breast cancer subtype. Citation Format: Ming-Feng Hou, Sheau-Fang Yang, Yu-Chun Huang, Fang-Ming Chen, Yao-Tsung Yeh. The cross-talk between nuclear p-ser294-FOXO3a and cytoplasmic MMP-2 in breast cancer survival and treatment response [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-08-16.

Abstract P4-10-20: Quality of life in Mexican young women with locally-advanced breast cancer: A cohort study

Abstract Background: Breast cancer (BC) is the most common malignancy and the leading cause of cancer-related deaths among young women worldwide. This population usually presents with more advanced stages at diagnosis compared to their older counterparts, exposing them to more intensive treatments which compromise their quality of life (QOL). This study aims to determine the change in QOL in young women with locally-advanced BC over time. Methods: Women aged ≤40, newly diagnosed with locally-advanced BC from 2016 to 2020 at three cancer referral centers in Mexico and accrued in the Joven &amp; Fuerte cohort were included and asked to complete the EORTC QLQ-C30 and QLQ-BR23 questionnaires at diagnosis, six months, and one year follow-up. Differences in mean values were analyzed using repeated measures ANOVA tests. The Mauchly's test was employed to assess the assumption of sphericity and if violated the Huynh-Feldt correction was used. Adjustment of multiple comparisons was performed with the Bonferroni correction. Results: A total of 195 patients with a median age at diagnosis of 35 years (IQR: 32-38) were analyzed. Most patients (59%) were married or in a domestic partnership and the majority (60%) were housewives or unemployed. The distribution of clinical stages at diagnosis was: IIB (41%), IIIA (39%), IIIB (11%), and IIIC (10%). Regarding treatment modalities, most patients underwent mastectomy (n=111, 57%), neoadjuvant (n=103, 53%) or adjuvant chemotherapy (n=79, 41%), and adjuvant endocrine therapy (n=106, 54%). QLQ changes over time are shown in the Table. Most functional scales worsened significantly at six months. Although most of them improved at one year of follow-up, they did not reach baseline levels. Certain symptoms such as fatigue, insomnia, financial difficulties, and arm symptoms worsened from baseline. When analyzing QLQ changes according to the different treatment modalities (mastectomy vs lumpectomy), (neoadjuvant vs neoadjuvant/adjuvant vs adjuvant chemotherapy) and (receiving hormone therapy vs not) no significant differences were found in functional scales or BC symptoms over time. Conclusion: Young women with BC experience physical and psychological distress that negatively impacts their QOL. Several BC specific domains worsened from baseline, such as body imaging, sexual satisfaction, and arm symptoms. Thus, strategies aimed at addressing these specific areas are warranted. QLQ-C30 and QLQ-BR23 at baseline, six months and one yearMean (SEM)NumberBaselineSix monthsOne yearp valueQLQ-C30Global health status14277.76 (1.65)73.53 (1.81)78.46 (1.59)0.047Physical Functioning14290.09 (0.93)86.62 (1.16)89.20 (1.02)0.026Role Functioning14286.97 (1.53)80.16 (1.86)87.68 (1.37)&amp;lt;0.001Emotional Functioning14275.12 (1.72)75.47 (1.81)73.01 (1.89)0.419Cognitive Functioning14282.75 (1.75)76.88 (1.75)77.93 (1.78)0.012Social Functioning14284.04 (1.83)77.70 (1.98)80.40 (1.82)0.015Fatigue14223.79 (1.53)29.89 (1.61)26.21 (1.50)0.002Nausea and vomiting1428.22 (1.23)11.39 (1.49)5.87 (1.22)0.012Pain14222.18 (1.87)21.95 (1.92)21.13 (1.67)0.876Dyspnea14210.80 (1.81)14.55 (1.68)10.09 (1.37)0.085Insomnia14226.29 (2.33)30.75 (2.43)27.23 (2.28)0.278Appetite Loss1429.39 (1.35)11.50 (1.45)8.45 (1.27)0.203Constipation14216.67 (2.28)20.42 (2.23)16.43 (1.94)0.259Diarrhea1428.45 (1.39)8.45 (1.35)5.87 (1.22)0.233Financial Difficulties14232.86 (2.56)38.73 (2.55)35.92 (2.60)0.161QLQ-BR23Body Imaging14280.69 (2.05)74.77 (2.15)76.64 (2.12)0.029Sexual Functioning14231.81 (2.33)24.77 (1.97)30.16 (1.99)0.009Sexual Enjoyment6162.84 (3.90)50.82 (4.45)50.27 (3.71)0.012Future Perspective14252.35 (2.67)49.30 (2.76)54.23 (2.46)0.245Systemic Therapy Side Effects14222.64 (1.46)29.21 (1.45)17.00 (1.01)&amp;lt;0.001Breast Symptoms14223.65 (1.95)17.96 (1.58)22.52 (1.47)0.022Arm Symptoms14217.14 (1.52)16.12 (1.56)20.27 (1.54)0.063Upset by hair loss12922.48 (3.07)24.55 (3.10)5.17 (1.62)&amp;lt;0.001 Citation Format: Cynthia Villarreal-Garza, Bryan F Vaca-Cartagena, Andrea Becerril-Gaitan, Alejandra Platas, Melina Miaja, Fernanda Mesa-Chavez, Ana S Ferrigno, Alan Fonseca, Marlid Cruz-Ramos, Lucero Labra, Enrique Bargallo-Rocha, Alejandro Mohar. Quality of life in Mexican young women with locally-advanced breast cancer: A cohort study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-10-20.

Abstract P3-19-04: Minimal increases in tumor infiltrating lymphocytes despite excellent tumor responses after pre-operative accelerated partial breast irradiation in early stage ER+ breast cancer patients

Abstract Purpose/Objectives: Local immune activity as measured by tumor infiltrating lymphocytes (TILs) has been correlated with improved outcomes in triple negative breast cancer (TNBC) and HER2+ disease. Furthermore, increased TILs after pre-operative systemic therapy for TNBC are also correlated with improved outcomes. However, the role of TILs in predicting outcomes in ER/PR+ breast cancer is less well-established. Radiation therapy (RT) can enhance immune cell infiltration in various tumors. However, breast cancer RT is typically given post-operatively, limiting the ability to determine whether RT enhances the %TILs in breast tumors. Here we report %TILs and tumor responses after pre-operative accelerated partial breast irradiation (APBI) as part of a clinical trial to determine whether RT enhances %TILs and whether this correlates with RT response. Materials/Methods: A breast pathologist assessed blindly the % stromal TILs and % tumor cellularity in biopsy and post-RT surgical specimens for patients treated on an in-house pre-operative APBI trial in patients with ER/PR+ breast cancer (NCT02728076). Patients received APBI to 30 Gy in 5 fractions on non-consecutive days, followed by surgery after no less than 5 weeks. Correlation between %TILs and pathologic response was assessed. Results: Thirty-five patients were enrolled and completed treatment. Median age was 65 (50-80). All patients were clinically node-negative and ER/PR+; one was HER2+. Median MRI tumor size was 0.9 cm (0.4-2.1 cm); 54% were grade 2 and 46% grade 1. 23/35 patients had 21- or 70-gene recurrence scores (RS), with 1 high RS; 2 patients received adjuvant chemotherapy and 33/35 received endocrine therapy after surgery. Most patients demonstrated robust tumor responses to RT, with 16/35 (46%) having &amp;lt5% cellularity after RT. With a median cellularity at diagnosis of 40%, 27/35 (77%) had a &amp;gt;20% decrease in cellularity, with only 3 patients having no decrease (range 0-59%). All tumors had low levels of TILs (median 5%, range 1-20%). There was minimal change in %TILs from biopsy to surgery, with 10/35 (28%) patients having increase of TILs &amp;gt4%, 2/35 with an increase of 10%, 2/35 having a decrease of 10% and the remainder with no %TIL increase. There were no correlations between %TILs (at diagnosis or post-RT) and tumor response to RT or RS. Conclusions: Pre-operative APBI in ER/PR+ breast cancers did not significantly increase the %TILs after 5 weeks, despite leading to significant tumor responses as measured by % cellularity. Low %TILs were seen, with no more than a 10% TIL increase after RT. These findings suggest this RT dose and fractionation schedule causes only mild immune changes, as measured by TILs, in this mostly favorable cohort of ER/PR+ cancers. Alternatively, the timing of surgery may have missed maximum TIL levels. Further characterization of TILs along with further studies in similar cohorts and in other breast cancer subtypes are warranted and will be performed to examine the role of pre-operative RT on breast cancer immune responses. Citation Format: Adam Currey, Julie M Jorns, Nina Desai, Tracy R Kelly, Joseph Bovi, Amanda L Kong, Anubha Wadhwa, Eric Paulson, Carmen Bergom. Minimal increases in tumor infiltrating lymphocytes despite excellent tumor responses after pre-operative accelerated partial breast irradiation in early stage ER+ breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-04.

Abstract P1-17-06: Impact of body mass index on the efficacy of aromatase inhibitors in patients with metastatic breast cancer

Abstract Background: Aromatase inhibitors (AIs) are part of standard endocrine therapy for hormone receptor (HR)-positive breast cancer (BC) and are used in both adjuvant and metastatic settings. Since AIs work by inhibiting the conversion of androgens to estrogen in peripheral adipose tissue, the higher levels of estrogen in obese patients may lead to incomplete inhibition by AIs and influence their efficacy. A retrospective analysis of the ABCSG-12 trial found that overweight premenopausal patients with early-stage BC treated with anastrozole had a 60% increased risk of disease recurrence and more than doubling in risk of death compared with normal weight patients on anastrozole. Similarly, an exploratory analysis from the ATAC trial found that in post-menopausal women with early-stage BC, overall recurrence rates were lower in patients randomized to anastrozole versus tamoxifen but in women with body mass index (BMI) &amp;gt; 30, there was no significant difference in disease recurrence between anastrozole and tamoxifen. While these findings raise concern for the efficacy of adjuvant AI therapy in obese patients with early-stage BC, this has not yet been demonstrated in the metastatic setting. The aim of this study was to determine the impact of BMI on efficacy of AIs in patients with metastatic HR-positive BC. Methods: We performed a retrospective chart review of all female patients with metastatic HR-positive BC on an AI in first- or second-line settings and seen at our academic institution between 2001-2020. The primary endpoint was progression-free survival (PFS), defined as the time from start of AI to disease progression or death from any cause. PFS was compared across BMI groups using Kaplan-Meier curves and log-rank tests. Cox proportional hazards regression model was used for univariate and multivariate analyses. Results: We identified 219 patients who had received an AI in the first- or second-line settings for metastatic HR-positive BC and with documented information on BMI. The median age was 59 with 45% of patients White, 29% African American, 16% Hispanic/Latino, 5.5% Asian and remainder other/unknown. 32% (71) had HER-2 positive disease. 82% (179) were on an AI in the first-line setting. Overall, 53% were on letrozole, 42% on anastrozole and 5.5% on exemestane. Of the 219 patients, 56% (123) had a low BMI (defined as &amp;lt; 27 kg/m2) and 44% (96) had a high BMI (≥ 27 kg/m2; based on the Breast Cancer Weight Loss [BWEL] trial). The median PFS was 21.9 months (95% CI, 14.5 to 28.4) in the low BMI group versus 20.2 months (95% CI, 14.3 to 27.5) in the high BMI group with no statistically significant difference (p =0.73). There were 8 (6.5%) deaths in the low BMI group and 7 (7.3%) deaths in the high BMI group. Multivariate cox regression model did not demonstrate any significant impact of BMI on PFS when adjusting for age, race/ethnicity, HER2 status, type of AI, line of therapy, drug partner and type of metastatic disease (HR =0.91, 95% CI =0.64 to 1.30, p =0.6 for high BMI group). Subgroup analysis of patients on an AI in the first line setting also did not show a significant difference in PFS with median PFS 19.3 and 18 months in the low and high BMI groups, respectively. Conclusions: In patients on an AI for metastatic HR-positive breast cancer, there was no statistically significant difference in PFS in patients with low versus high BMI. While BMI influences efficacy of AIs in the adjuvant setting, our results demonstrate that in the metastatic setting, BMI does not significantly impact the efficacy of AIs among our patient population. This discrepancy could be due to other differences in disease characteristics that make complete aromatase inhibition more important in the adjuvant setting when disease burden is the lowest. Additional larger studies are needed to confirm this finding. Citation Format: Rima Patel, Zhiqiang Li, Brittney S. Zimmerman, Marc Y. Fink, Jason D. Wells, Xiang Zhou, Kristin L. Ayers, Arielle Redfern, Scott Newman, Rong Chen, William K. Oh, Amy Tiersten. Impact of body mass index on the efficacy of aromatase inhibitors in patients with metastatic breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-17-06.

Abstract P4-05-15: Follow-up of prospective cohort of Mexican premenopausal women with breast cancer who received guided adjuvant treatment with the EndoPredict assay

Abstract Background: Choosing the appropriate treatment for patients with early hormone receptor (HR)-positive and HER2-negative breast cancer (BC) remains a challenging process that must balance possible therapy benefits against potential side effects. Recent reports on premenopausal patients raise concerns about the safety of omitting chemotherapy (CT), and no consensus has been reached to define the use of these tools in the decision-making process. Thus, further research is needed to guide the use of genomic testing on this young group. Due to the limited data of the EndoPredict (EP) assay performance in premenopausal women, we aim to describe the follow-up results of a prospective cohort that utilized the EP assay to guide adjuvant treatment decision-making in this group of patients. Methods: Premenopausal women with HR-positive, HER2 negative, T1-T2, and N0-N1 BC who received adjuvant treatment guided by the results of the EP assay in two referral BC centers in Mexico were included. Clinicopathological and genomic characteristics were collected. Recurrence-free survival (RFS) and distant disease-free survival (DDFS) were evaluated using the Kaplan-Meier estimate. The Chi-squared and Log-rank tests were employed for group comparisons. Results: A total of 99 patients with a median age at diagnosis of 43 years (IQR 39-46) were analyzed. Most patients had T2 (54%), node-negative disease (72%), and low/intermediate-grade disease (85%). The distribution of clinical stages at diagnosis was: IA (38%), IB (2%), IIA (37%), IIB (22%). Regarding EPclin scores, 54% patients were categorized as high-risk while 47% had low-risk of distant recurrence. With respect to CT, 15% of patients in the low-risk group received CT compared to 100% in the high-risk category (p&amp;lt;0.001). Only 9% of patients received hormone therapy (HT) along with ovarian suppression mainly due to financial restrictions. Median follow-up for the entire cohort was 39 months (IQR 33-50). In total, 7 patients experienced disease recurrence: 3 in the low-risk and 4 in high-risk EPclin groups; data are shown in the table. Of the recurrences, 4 (57%) were local/regional and 3 (43%) were distant. Of note, all 3 recurrences experienced by patients assigned to a low-risk category were local/regional. Remarkably, all patients with recurrent disease received HT only with tamoxifen. Regarding sites of distant metastasis, 1 was visceral, 1 was non-visceral, and the other was mixed (visceral and non-visceral). At 48 months, patients with low-risk and high-risk EP had a RFS of 89.8% (95CI 78.04%-100%) and 92.1% (83.08-100%), respectively. Regarding DDFS, at 48 months the low-risk EP group had no events recorded, while DDFS for the high-risk group was 94.2% (95%CI 85.97-100%), (p=0.094). One patient in the high-risk group has died up to this follow-up. Conclusion: In this cohort, the use of EP as a guidance for treatment decision-making proved to be an effective tool as patients with low-risk EP in whom CT was omitted did not have an increased risk of distant recurrence. Moreover, patients with high-risk EP scores had a not significant worse DDFS compared with those with low-risk EP, possibly accounting for patients not receiving the most optimal HT. A longer follow-up is required to monitor recurrence events and survival. Further studies are warranted for assessing EP and other genomic signatures’ impact in CT de-escalation and survival among premenopausal women. Clinicopathological characteristics of patients with recurrent disease.Age (y) at diagnosisStage (pT pN)GradeER (%)PR (%)Ki67 (%)EP resultEPclin scoreCTHTType of recurrence37IIA (T2 N0)29595N/ILow risk2.7NoTamoxifenLocal/regional43IA (T1c N0)2802010Low risk2.9NoTamoxifenLocal/regional45IA (T1c N0)21006020Low risk3.2NoTamoxifenLocal/regional42IIA (T2 N0)N/I1007040High risk3.9YesTamoxifenLocal/regional38IIA (T2 N0)2704040High risk4.2YesTamoxifenDistant35IIB (T2 N1)2604010High risk4.4YesTamoxifenDistant41IIB (T2 N1)2909070High risk5.1YesTamoxifen (after CT-induced ovarian failure)DistantER= Estrogen receptor status. PR= Progesteron receptor status. N/I= No information. Citation Format: Daniela Vazquez-Juarez, Bryan F Vaca-Cartagena, Andrea Becerril-Gaitan, Zuratzi Deneken-Hernandez, Ana S Ferrigno, Antonio Maffuz-Aziz, Edna A Lopez-Martinez, Regina Barragan-Carrillo, Jose F Muñoz-Lozano, Cynthia Villarreal-Garza. Follow-up of prospective cohort of Mexican premenopausal women with breast cancer who received guided adjuvant treatment with the EndoPredict assay [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-05-15.

Abstract P5-13-13: PIK3CA mutations co-occurring with copy number gain identify patients with adverse outcome and potentially different treatment sensitivity among hormone receptor positive and HER2 negative metastatic breast cancer

Abstract INTRODUCTION: Somatic mutations of the PIK3CA gene, encoding for the class IA PI3K p110α subunit, are the most common activating mutations in breast cancer (BC), occurring in 30-50% of early and in 28% of metastatic ER+/HER2- disease. We have previously demonstrated that PIK3CA mutations co-occurring with copy number (CN) gain (PIK3CA-mut/gain) are associated with worse outcome in patients with early hormone receptor positive and HER2 negative (HR+/HER2-) BC, including those receiving endocrine therapy (ET). Here we aim to evaluate the prognostic role of PIK3CA-mut/gain in patients with metastatic HR+/HER2- BC treated with chemotherapy, ET alone or in combination with targeted therapies (CDK4/6 inhibitors or everolimus) included in a publicly available dataset of BC. PATIENTS AND METHODS: We accessed genomic, clinical, treatment and outcome data from 1365 patients with HR+/HER2- BC included in the MSK-2018 dataset. Patients treated for distant metastases were selected. PIK3CA status, considering both protein-affecting mutations and CN alterations, was derived from pre-treatment biopsies data. Tumors were classified as: PIK3CA wt and CN neutral (-wt/neut), PIK3CA wt with CN gain (-wt/gain), PIK3CA mutant and CN neutral (-mut/neut), and PIK3CA mutant with CN gain (-mut/gain). Tumors with PIK3CA loss were excluded from the analyses. For each patient and treatment type, only progression free survival (PFS) from the first available line of treatment was analyzed, thus excluding data concerning possible retreatments with the same drug in subsequent lines. Multivariate Cox proportional hazard models were used to assess the association between PIK3CA status and PFS including treatment line and the four categories of PIK3CA as co-variates. RESULTS: The proportion of PIK3CA-mut/gain was 15.4% in the chemotherapy group (n=454), 17.3% in the ET alone group (n= 352), 13.4% in the ET plus CDK4/6 inhibitors group (n= 268) and 10.5% in the ET plus everolimus group (n= 143). As expected, in all groups treatment line was significantly and independently associated with PFS. In the ET alone group, patients whose tumors had gain in PIK3CA CN, with or without co-occurring mutations, were at significantly higher risk of progression compared with PIK3CA-wt/neut (HR 2.2 [1.53-3.2] p&amp;lt;0.001 for PIK3CA -mut/gain; HR 1.5 [1.03-2.2] p= 0.034 for PIK3CA-wt/gain), while PIK3CA-mut/neut status was not significantly associated with progression (HR 1.2 [0.87 − 1.6] p= 0.289). Similar observations, without reaching statistical significance, were also made in the CDK4/6 inhibitors group (HR 1.6 [0.92-2.6] p= 0.099 for PIK3CA-mut/gain; HR 1.6 [0.97-2.5] p= 0.068 for PIK3CA-wt/gain) and in the chemotherapy group (HR 1.4 [0.98-2] p= 0.063 for PIK3CA-mut/gain; 1.2 [0.89-1.6] p= 0.223 for PIK3CA-wt/gain). On the other hand, in patients treated with ET plus everolimus, while there was a borderline significant increased risk of progression for patients with PIK3CA-wt/gain tumors (HR 1.8 [1.00 − 3.3] p= 0.051) and for those with PIK3CA-mut/neut (HR 1.6 [0.98-2.5) p= 0.06), this was not observed in patients with PIK3CA-mut/gain tumors (HR 1.1 [0.5-2.2] p=0.89), potentially suggesting a treatment benefit. CONCLUSIONS: Our data suggest that patients with metastatic HR+/HER2- BC with tumors with PIK3CA-mut/gain have poor outcome. These data are in line with our previous report in patients with early BC. Further studies are warranted to understand if patients with PIK3CA-mut/gain tumors might benefit from the combination of ET and everolimus. Citation Format: Ilenia Migliaccio, Marta Paoli, Emanuela Risi, Chiara Biagioni, Laura Biganzoli, Matteo Benelli, Luca Malorni. PIK3CA mutations co-occurring with copy number gain identify patients with adverse outcome and potentially different treatment sensitivity among hormone receptor positive and HER2 negative metastatic breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-13-13.

Reference intervals for biochemical analytes in transgender individuals on hormone therapy.

Hormone therapy in transgender individuals may impact processes that lead to changes in biochemical analytes, and therefore reference intervals. Currently, few reference interval studies are available for the transgender population. We determined biochemical reference intervals for transgender individuals receiving hormone therapy. Our retrospective, laboratory-based, observational study included healthy transgender males (N = 24) and transgender females (N = 84) on hormone therapy. Various biochemical reference intervals were established for each cohort and compared to their cisgender counterparts. We detected significant differences in reference intervals for sodium, 139-142mmol/L vs. 136-145mmol/L when comparing transgender males (TM) with cisgender males (CM). The following significant changes in upper reference limits (URL) for TM versus CM were detected, ALP (URL: 96 U/L vs. 128 U/L), GGT (URL: 27 U/L vs. 67 U/L) and testosterone (URL: 46.7nmol/L vs. 29.0nmol/L), respectively. Moreover, when comparing transgender female (TF) to cisgender female (CF), significant differences in creatinine (URL: 117μmol/L vs. 90μmol/L), albumin (lower reference limit: 41g/L, vs. 35g/L), AST (URL: 50 U/L vs. 35 U/L), ALP (URL: 118 U/L vs. 98 U/L) and oestradiol (URL: 934 pmol/L vs. 213 pmol/L) were noted, respectively. Significantly higher LDL-C was observed for TM on hormone treatment, compared to baseline (2.9mmol/L vs. 2.2mmol/L, p <0.01). Biochemical results for TM and TF receiving hormone therapy can be evaluated against our transgender-specific reference intervals for some analytes, while others can be compared to their identified gender reference intervals.

Safety of adjuvant CDK4/6 inhibitors during the COVID-19 pandemic.

Safety of adjuvant CDK4/6 inhibitors during the COVID-19 pandemic.

Menopause-related medication use among women age 45-75 experiencing incarceration in North Carolina 2015-2016

PurposeThis study aims to estimate the prevalence of individuals receiving hormone therapy for menopause management and the prevalence of underlying conditions that may constrain options for pharmacologic menopause management in the prison context.Design/methodology/approachThis study reviewed all prescriptions dispensed by the North Carolina Department of Public Safety between July 1, 2015, and June 30, 2016, for relevance to menopause management. Relevant medications were those either recommended for menopause management or those indicated for management of conditions that may complicate menopause management, as per the 2015 clinical decision-support algorithm tool developed by the North American Menopause Society. Analysis was restricted to women between the ages of 45 and 75.FindingsOf 1,120 women, a majority (77.8%) were between the ages of 45 and 54. Less than 5% of individuals in this study were prescribed estrogen-containing therapy. The most commonly prescribed medications that may constrain options for menopause treatment were related to hypertension and other cardiovascular disease or mental health conditions.Research limitations/implicationsThe retrospective nature of this data set limits the findings, given that researchers did not have access to diagnoses or data on polypharmacy. Still, this study indicates that many women over 45 experiencing incarceration are living with health conditions that may complicate menopause symptom management with hormone therapy. Future research in carceral settings must examine the prevalence of menopause-related symptoms as well as access to and quality of comprehensive menopause management.Originality/valueThere is a paucity of literature around the menopause-related needs of individuals experiencing incarceration. To the best of the authors’ knowledge, no other research has examined prevalence of pharmacologic menopause management among women who are incarcerated.

Primary low-grade extrauterine endometrial stromal sarcoma: analysis of 10 cases with a review of the literature

BackgroundThis study aimed to analyze the clinical and pathological features of extrauterine endometrial stromal sarcoma (EESS) and explore an effective therapeutic regimen to reduce the recurrence rate in low-grade EESS patients.MethodsTen LG-EESS patients who were treated at the Chinese Academy of Medical Sciences Cancer Institute and Hospital from June 1999 to June 2019 were collected and analyzed.Results(1) Patient demographics are summarized in manuscript. Preoperative CA125 examination showed that 8 patients had a median level of 49.5 U/L (15.4–168.0 U/L). (2) All ten patients underwent tumor cytoreductive surgery. Five patients underwent optimal tumor resection and achieved an R0 resection. After the initial surgery, 7 patients who had multiple metastasis were treated with adjuvant chemotherapy, 2 patients with vaginal ESS were treated with chemotherapy and radiation therapy, and 6 patients with ER/PR positive received hormone therapy with or without chemotherapy. (2) Most EESS patients had multiple tumors. The omentum was the most commonly affected site, followed by the ovaries. (3) The median follow-up was 94 (range: 27–228) months, and recurrence was observed in 3 patients (n = 10, 30%) who underwent non-optimal surgery and no hormone therapy. The 5-year and 10-year DFS rates were both 70%, as shown in Fig. 2. OS was both 100% at 5 and 10 years.ConclusionAs a conclusion, EESS is a rare disease and LG-EESS has a good prognosis. Surgery remains the available treatment for patients. LG-EESS has a risk of late recurrence which requires a long-term follow-up. With a limited sample size, our study shows optimal tumor reductive surgery and adjuvant hormone therapy may significantly reduce the risk of recurrence.

Clinical value of next-generation sequencing in guiding decisions regarding endocrine therapy for advanced HR-positive/HER-2-negative breast cancer

The mechanism of acquired gene mutation plays a major role in resistance to endocrine therapy in hormone receptor (HR)-positive advanced breast cancer. Circulating tumor DNA (ctDNA) has been allowed for the assessment of the genomic profiles of patients with advanced cancer. We performed this study to search for molecular markers of endocrine therapy efficacy and to explore the clinical value of ctDNA to guide precise endocrine therapy for HR-positive/human epidermal growth factor receptor-2 (HER-2)-negative metastatic breast cancer patients. In this open-label, multicohort, prospective study, patients were assigned to four parallel cohorts and matched according to mutations identified in ctDNA: 1) activation of the phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway preferred mTOR inhibitor combined with endocrine therapy; 2) estrogen receptor 1 (ESR1) mutation preferred fulvestrant; 3) HER-2 mutations preferred pyrotinib; and 4) no actionable mutations received treatment according to the clinical situation. In all cohorts, patients were divided into compliance group and violation group. The primary outcome measure was progression-free survival (PFS), and the secondary outcome measure was overall survival (OS). In all cohorts, the combined median PFS was 4.9 months, and median PFS for the compliance and violation groups was 6.0 and 3.0 months, respectively [P=0.022, hazard ratio (HR)=0.57]. Multivariate Cox regression model showed the risk of disease progression was lower in compliance group than in violation group (P=0.023, HR=0.55). Among the patients with HER-2 mutations, the median PFS was 11.1 months in the compliance group and 2.2 months in the violation group (P=0.011, HR=0.20). There was no significant difference in the median PFS between patients who did and did not comply with the treatment protocol in patients with activation of the PI3K/AKT/mTOR or ESR1 mutation. The results suggest that ctDNA may help to guide the optimal endocrine therapy strategy for metastatic breast cancer patients and to achieve a better PFS. Next-generation sequencing (NGS) detection could aid in distinguishing patients with HER-2 mutation and developing new treatment strategies.

Assessment of body mass index and its relationship with breast cancer survival in a clinical oncology service in the Federal District

OBJECTIVE: The purpose of this study was to analyze the relationship between obesity and clinical outcomes in breast cancer patients by evaluating the mean body mass index (BMI) and overall survival. MATERIAL AND METHODS: The research's method consisted of a retrospective observational and descriptive study without intervention, carried out in a public oncology service in Brazils Federal District. We selected breast cancer patients with hormonal expression positivity in follow-up from January 2016 to December 2020. RESULTS: 305 female patients were evaluated, aged between 33 and 92 years old (average age of 59). Most patients were over 55 years old (63.3%). The mean weight of the patients was 71.70±9.10 kilograms. Regarding BMI, 38.7% of patients were classi?ed as obese. As for the immunohistochemical classi?cation (IHC), 72.9% of the patients were luminal B. Among the patients in which the initial treatment was registered, 56.1% received hormone therapy, while 43.9% received chemotherapy. The intention to treat in most patients was curative. Most patients had disease staging between II and III. As for the outcome, most patients were still undergoing treatment (83.0%) at the time of data collection. Correlating the IHC classi?cation with patient survival, there was no signi?cant difference between patient's classi?ed as luminal A and those classi?ed as luminal B (p: 0.342). There was also no signi?cant difference between non-obese and obese patients in the assessment of overall survival and weight (p: 0.917). CONCLUSION: Despite the high prevalence of obesity in the studied population, the overall survival of this group did not differ from the non-obese group, even in the analyzes by IHC pro?le.