Received Hormone Therapy Research Articles

Prostate Cancer in Male-to-Female Transgender Individuals: Histopathologic Findings and Association With Gender-affirming Hormonal Therapy.

Male-to-female (MtF) transgender individuals are at risk for prostate cancer, although guidelines for screening and management in this population are not well established. We describe a series of 9 MtF transgender patients who underwent prostate tissue sampling and highlight histopathologic features and challenges related to pathologic interpretation of prostate tissue in this patient population. Seven of 9 total patients were diagnosed with prostate cancer and all had elevated prostate-specific antigen at the time of diagnosis. Three of the 7 patients diagnosed with prostate cancer had received different types of hormone therapy for gender affirmation before the diagnosis of prostate cancer, and in all 3 of these patients, there was histologic evidence of hormone therapy effect in both benign prostate tissue and/or the adenocarcinoma. The 2 patients with benign prostate tissue underwent transurethral resection for lower urinary tract symptoms and were previously on hormone therapy for gender affirmation. Both of these specimens showed diffuse glandular atrophy and basal cell hyperplasia, indicative of hormone therapy effect on benign prostatic tissue. In the patients diagnosed with prostate cancer, a spectrum of grades was observed, ranging from Grade Group 1 to Grade Group 5. Four patients underwent radical prostatectomy, with 2 cases showing extraprostatic extension and Grade Group 5 prostatic adenocarcinoma, and 2 showing Grade Group 2 prostatic adenocarcinoma. Three of the 4 patients who underwent radical prostatectomy had received gender-affirming hormone therapy before surgery, and all 3 of these specimens showed hormone therapy effect in non-neoplastic prostate tissue and focal hormone therapy effect in prostatic adenocarcinoma. The presence of areas of viable carcinoma without hormone therapy effect enabled the assignment of a Gleason score and Grade Group in these 3 cases. Hormone therapy administered for gender identity affirmation induces histopathologic changes to both benign prostate tissue (nonkeratinizing squamous metaplasia, diffuse atrophy, basal cell hyperplasia, and stromal dominance with decreased numbers of glands) and prostatic adenocarcinoma (nuclear pyknosis, atrophy, cytoplasmic vacuolization, and architectural patterns that would qualify for Gleason 4 and 5 in the absence of hormone therapy effect) that have been traditionally seen in cis-male prostate cancer patients receiving hormone therapy. In the absence of hormone therapy, the morphology of prostatic adenocarcinoma in transgender patients shows classic morphologic features similar to those seen in cis-male patients not on hormone therapy. Prostate cancer with hormone therapy effect may not only be histologically quite subtle and may be overlooked if not suspected, but also should not be assigned a Gleason score because the Gleason score would substantially overstate its biologic potential. Therefore, similar to cis-male patients who have received androgen deprivation therapy for prostate cancer, transgender patients on hormone therapy for gender affirmation may be at risk for both underrecognition and over-grading of prostate cancer, particularly if the pathologist is not aware of the clinical history.

Patterns of Care and Utilization of Radiation for Women With Good-Risk Ductal Carcinoma In Situ: A National Cancer Database Analysis.

Purpose/objective(s)Lumpectomy followed by whole-breast radiation therapy (WBRT) provides a 50% recurrence rate reduction in ductal carcinoma in situ (DCIS) patients when compared to lumpectomy alone. Certain factors increase the risk of recurrence, including higher nuclear grade, large size, age less than 50, and close margins. RTOG 9804 demonstrated a reduction in local failure after WBRT with the use of adjuvant radiation in women with "good-risk disease" (mammographically detected, measuring less than or equal to 2.5 cm, with a predominant nuclear grade of 1 or 2, and a margin of greater than or equal to 1 cm, or a negative re-excision). The purpose of this study is to retrospectively identify the patterns of care in women with low-risk DCIS utilizing the National Cancer Database (NCDB). We hypothesize that with the utilization of hypofractionation, there may be an increase in the delivery of RT for these "good-risk" patients.Materials/methodsThe National Cancer Database was queried to identify women treated with lumpectomy for <2.5 cm, nuclear grade 1 or 2 DCIS of the breast from 2004 to 2016. Data were collected regarding age, tumor size, endocrine therapy use, ER receptor status, race, insurance type, and distance from the treatment center. The distance was stratified into quartiles consisting of 0-3.9, 4-8, 8.1-15.8, and > 15.8 miles, respectively. Radiation fractionation was collected and categorized as hypofractionation, standard fractionation, or other if fractionation could not be ascertained. Clinical and patient-related factors were compared between patients who received radiation and those who received no radiation. The frequency distributions between categorical variables were compared using the Chi-square test. Multivariable logistic regression was used to identify covariables that impacted the receipt of radiation.ResultsThe eligibility criteria were met by a total of 12,846 patients. Of those, 6,600 (51.4%) received adjuvant WBRT. On multivariable regression, patients whose tumors were ER (OR 1.24, P<0.001) and those who had not received endocrine therapy (OR 2.24, P<0.001) were more likely to receive WBRT. Factors less likely to receive WBRT included increasing age over 50 (age 50-65 OR 0.83, P<0.001; age>65 OR 0.58, P<0.001), and distance of >15.8 miles (OR 0.78, P<0.001). The fractionation technique was categorized as standard or hypofractionated in 52.2% of patients. Of those, the use of hypofractionation increased from 0.4% in 2004 to 8.9% in 2010 and to 53.8% in 2016.ConclusionThis NCDB analysis demonstrated that patients who meet the RTOG 9804 criteria for "good-risk" DCIS are less likely to receive RT as time progresses despite an increase in the utilization of hypofractionation techniques. Overall, slightly more than half of these patients receive adjuvant RT.

Dual function miR-205 is positively associated with ER and negatively with five-year survival in breast cancer patients

BackgroundPrecise molecular characterization of breast cancer, especially triple negative (TNBC) as the most lethal subtype, is needed to stratify patients for the individual treatment approach. MicroRNA-205 (miR-205) has tumor-suppressive and oncogenic functions across different cancers. Therefore, miR-205 might have a different role in TNBC and estrogen receptor (ER) positive BC. Our aim was to investigate how miR-205 expression is associated with ER/progesteron receptor status, clinical parameters, pathohistological characteristics of BC, and survival of patients MethodsWe determined miR-205 relative expressions in 73 primary breast tumors (50 TNBC and 23 ER+) by quantitative Real-time polymerase chain reaction (qPCR) and compared it to clinicopathological characteristics and outcome. ResultsThe highest levels of miR-205 were in the ER+ /PR+ group, and the lowest in the TNBC group (p = 0.009). Significantly higher levels of miR-205 were also observed in the ER+ compared with the ER-negative group, regardless of the PR status (p = 0.002). Low miR-205 expression level was associated with prognostic stage III in TNBC samples (p = 0.049). Patients who received adjuvant chemotherapy had significantly lower levels of miR-205 (p = 0.016). Patients who received hormone therapy had significantly higher levels of miR-205 (p = 0.007). The low-miR-205 patients had significantly higher 5-year survival rates (p = 0.041). ConclusionThe expression of miR-205 in BC is subtype-specific and high expression is associated with the ER+ tumors. The miR-205 expression might be a useful marker of TNBC progression. High miR-205 expression had a detrimental effect on BC patient outcome. Our results indicate that miR-205 might be utilized in clinical practice as a biomarker and an adjunct parameter for the selection of the most effective therapeutic modality.

CLINICO-HISTOPATHOLOGICAL STUDY OF ENDOMETRIUM WITH AND WITHOUT HORMONE THERAPY IN PATIENTS WITHABNORMAL UTERINE BLEEDING

Background: Abnormal uterine bleeding (AUB) is one of the most common problem for the patients and the gynecologists. Histological characteristics of endometrial biopsy material as assessed by light microscopy remains the diagnostic standard for the diagnosis of endometrial pathology. Material and Methods: In our prospective study of 100 patients of the age between 24-75 years, clinical characteristics and the pattern of endometrial histopathology and their association with hormone therapy administration were studied. Results: Total of 100 patients were divided into two subgroups one that received hormone therapy prior to endometrial biopsy and Group II in which hormone therapy was not administered prior to the said procedure. In both groups proliferative phase was the commonest followed by secretory endometrium in both groups. Pill change, Arias Stella reaction, tubercular endometritis, endometrial carcinoma was exclusively noted in the group in hormone therapy was administered prior to endometrial biopsy. Pill change endometrium was only significantly correlated with Group I (p=0.05). Simple hyperplasia, endometrial polyp, chronic endometritis, endocervical polyp, atrophic endometrium was noted in Group II of which simple hyperplasia (p=0.10) was not found to be clinically significant. Conclusions: The study of the endometrium in AUB revealed many structural and non-structural causes manifest in the form of different endometrial histopathological patterns in two groups with or without hormone therapy. Endometrial study gives significant etiological information in AUB when interpreted with relevance to age and other clinical data, thus guiding the appropriate management.

Hormone Therapy Reduces Recurrence in Stage II-IV Uterine Low-Grade Endometrial Stromal Sarcomas: A Retrospective Cohort Study.

Low-grade endometrial stromal sarcoma (LG-ESS) is a rare and indolent malignancy. Hormone therapy has been reported as an adjuvant treatment for LG-ESS, although its effectiveness is controversial. Here we aimed to investigate the effects of postoperative hormone therapy on recurrence in patients with uterine LG-ESS. Between January 2010 and December 2019, a total of 152 patients (23 with and 129 without fertility-sparing) with a diagnosis of primary uterine LG-ESS confirmed by pathologists were enrolled in this study. In the cohort without fertility-sparing, 22 (17.7%) patients had recurrence, and the median disease-free survival (DFS) was 47 (2-130) months; only one of these patients died of LG-ESS. No significant difference was found in recurrence between the groups with and without hormone therapy (p=0.802). However, subgroup analysis showed that hormone therapy decreased the recurrence rate in stage II-IV (p=0.001, HR 0.144, 95% CI: 0.038-0.548), but not in stage I disease (p=0.256). High-dose progestins notably reduced recurrence (p=0.012, HR 0.154, 95% CI: 0.036-0.660), whereas non-progestin therapy marginally influenced recurrence (p=0.054) compared with no hormone therapy in stage II-IV disease. Moreover, hormone therapy within 12 months was effective in reducing recurrence (p=0.038, HR 0.241, 95% CI: 0.063-0.922). Ovarian preservation (p=0.004, HR 6.250, 95% CI: 1.786-21.874) and negative expression of ER/PR (p=0.000, HR 23.249, 95% CI: 4.912-110.026) were high-risk factors for recurrence in patients without fertility-sparing. In the fertility-sparing cohort, 15 (65.2%) patients experienced recurrence, and the median DFS was 24 (3-107) months. Six patients successfully delivered healthy fetuses, and five received hormone therapy. Twelve patients finally accepted hysterectomy after repeated recurrence, and only two of them had given birth before surgery. Patients who received hormone therapy showed longer DFS, although this difference was not statistically significant (p=0.466). In conclusion, postoperative hormone therapy reduces recurrence in patients with stage II–IV uterine LG-ESS without fertility-sparing, and high-dose treatment with progestins within 12 months is recommended. Bilateral oophorectomy can also reduce the risk of recurrence. Patients with fertility-sparing have a high risk of recurrence and poor pregnancy outcomes, and hormone therapy may be a reasonable choice in postoperative management.

Assessing Fertility Intentions in Patients Presenting for Gender-Affirming Surgery.

Purpose: For some transgender and gender-diverse (TGD) individuals, gender-affirming surgery may represent the last opportunity to engage in gamete banking (GB) and other forms of fertility preservation (FP). Previous research has assessed fertility intentions among TGD people initiating hormone therapy. The objective of this study was to describe the fertility intentions of patients seeking gender-affirming surgery. Methods: A retrospective chart review was conducted for 233 patients seeking chest or genital surgery between 2017 and 2019. Data abstracted included interest in having children (biological or non-biological) and GB, and barriers to FP. Associations between fertility intentions, sex assigned at birth, and surgical procedure sought were assessed. Results: Of the 233 records reviewed, 162 (70%) documented information about fertility intentions for patients without a history of sterilizing surgery. At initial consultation, 94% were receiving hormone therapy. Among the 60 patients seeking genital surgery, 30% expressed interest in GB and 38% were not interested in biological children. Among the 102 patients seeking chest surgery, 11% expressed interest in GB and 47% were not interested in biological children. Patients assigned male at birth were more likely to have already completed GB (p < 0.001). Among the patients interested in FP, 41% reported barriers to access. Conclusion: Many TGD people in our study expressed no interest in biological parenthood; however, 30% of patients seeking genital surgery expressed interest in GB. This suggests that some who defer FP when starting hormones may wish to pursue it later in life. Ongoing assessment of fertility intentions and reducing barriers to FP are integral to caring for TGD people.

Hormone therapy and fractures in postmenopausal women.

Fracture rates have been reported to be higher among older women living with HIV (WLWH) than HIV- women. Hormone therapy with estrogen can reduce vasomotor symptoms (VMS) associated with menopause and prevent fractures. As data are limited on the benefits of hormone therapy use in WLWH, we examined associations of hormone therapy, use and fractures. A prospective study of 1765 (1350 WLWH and 415 HIV-) postmenopausal Women's Interagency HIV Study (WIHS) participants was performed, including self-reported hormone therapy, use and fracture data from 2003 to 2017. Proportional hazard models determined predictors of new fractures at any site or at typical fragility fracture sites (hip, spine, wrist). At the first postmenopausal visit, the median (IQR) age of WLWH was slightly younger than HIV- women [49.8 (46.4-53) vs. 50.7 (47.5-54), P = 0.0002] and a smaller proportion of WLWH reported presence of VMS (17% vs. 26%, P < 0.0001). A greater proportion of WLWH than HIV- women reported hormone therapy use (8% vs. 4%, P = 0.007) at the first postmenopausal visit. In multivariate analyses, white race and smoking were significant predictors of incident fracture at any site but hormone therapy ( P = 0.69) and HIV status ( P = 0.53) were not. Our study did not find evidence of benefit or harm with regards to fracture outcomes in postmenopausal WLWH receiving hormone therapy. Further research is needed to determine whether hormone therapy has benefits beyond treatment of VMS, such as prevention of adverse aging-associated outcomes.

Clinicopathological Features of 166 Cases of Invasive Ductal Breast Carcinoma and Effect of Primary Tumor Location on Prognosis after Modified Radical Mastectomy.

Objective To investigate the clinicopathological features of 166 cases of invasive ductal carcinoma (IDC) of the breast and to analyze the effect of the location of the primary tumor on the prognosis of modified radical mastectomy. Materials and Methods The clinical data of 166 patients with IDC who underwent modified radical mastectomy in our hospital from May 2015 to May 2017 were retrospectively analyzed. The clinicopathological features of IDC patients were recorded. Univariate analysis and the multivariate logistic regression model were used to analyze the relationship between the location of the primary tumor and the prognosis of IDC patients after modified radical surgery. The effect of primary tumor location on the prognosis of modified radical resection was used with Survival curve analysis. Results Among the patients in the central region, 13.33% had tumors >5 cm in diameter, which was higher than those in the other four groups. Among the patients in the upper inner quadrant, 59.38% received hormone therapy after operation, which was higher than those in the other four groups (P < 0.05). There were no significant differences in age, menopause, histological grading, molecular typing, lymph node metastasis, vascular invasion, radiation therapy, and chemotherapy among different groups (P > 0.05). Univariate analysis showed that molecular typing, lymph node metastasis, vascular invasion, and location of the primary tumor were all related to the prognosis of IDC patients after modified radical surgery, and the differences were statistically significant (P < 0.05). Logistic regression analysis showed that molecular typing, lymph node metastasis, vascular invasion, and primary tumor location were all independent influencing factors for prognosis of IDC patients after modified radical surgery (P < 0.05). As of 31 May 2021, there were 11 patients with recurrence and metastasis and 20 patients with death. The median survival time in the outer upper quadrant group was 80 months, which was higher than that in the outer lower quadrant group by 72 months, the median survival time in the central region group by 71 months, the median survival time in the inner upper quadrant group by 67 months, and the median survival time in the inner lower quadrant group by 61 months. The log-rank test showed all P < 0.001. Conclusion Patients with primary tumors located in the central area have larger tumor diameters. Patients located in the central area, upper inner quadrant, and lower inner quadrant are more likely to have lymphatic metastasis, have a more serious condition, and have a shorter prognosis survival time. Unluminal type, multiple lymph node metastases, vascular invasion, and the location of the primary tumor in the inner quadrant are all independent risk factors for prognosis in patients after modified radical surgery for IDC.

Clinical value of next-generation sequencing in endocrine therapy for advanced hormone receptor–positive/HER2-negative breast cancer.

1062 Background: Acquired gene mutation is a major mechanism of resistance to endocrine therapy in hormone receptor (HR)-positive advanced breast cancer. Circulating tumor DNA (ctDNA) facilitates the current assessment of the genomic profile in patients with advanced cancer. We performed this clinical trial to determine the landscape of gene mutation before endocrine therapy, to search for molecular markers of endocrine therapy efficacy, and to explore the clinical value of ctDNA to guide precise endocrine therapy in patients with advanced breast cancer. Methods: We conducted an open-label, single-center, multicohort, prospective study. Patients were women with pathologically and immunohistochemically confirmed HR-positive/HER-2-negative patients with advanced breast cancer. Patients relapsed during or after adjuvant endocrine therapy or progressed after completing at least one previous line of treatment for advanced breast cancer. Patients were assigned to four parallel treatment cohortsmatched to mutations identified in ctDNA: 1) cohort A comprised patients with abnormal activation of PI3K/Akt/mTOR pathway signal, preferred mTOR inhibitor combined with endocrine therapy; 2) cohort B comprised patients with ESR1 mutation and who did not use fulvestrant before, preferred fulvestrant; 3) cohort C comprised patients with HER2 mutations, preferred pyrotinib combined with endocrine therapy; 4) cohort D comprised patients with no significant gene mutation, making treatment plan according to the actual clinical situation. If more than one mutation was identified, the priority of entry is cohorts C, cohorts A and cohort B. In the A-D cohort, patients who obey the treatment plan are the compliance group, and patients who do not obey the treatment plan are the violation group. The primary endpoints were progression-free survival (PFS), and the secondary endpoints included overall survival time (OS). Results: A total of 113 patients underwent NGS detection of ctDNA, and 84 patients were enrolled in the study. In all cohorts, combined median PFS was 4.9 months, and the median PFS in the compliance group was 3.0 months longer than in the violation group (6.03 vs 3.03 months, p = 0.0222, HR = 0.5743, 95%CI 0.3273-1.007). In cohort C, the median PFS was 11.1 months in the compliance group and 2.22 months in the violation group (p = 0.0067, HR = 0.1980, 95%CI 0.032-1.22). There was no significant difference in the median PFS between patients with and without compliance with the treatment protocol in cohort A and cohort B (p = 0.5054 and 0.7325, respectively). Conclusions: The study suggested that ctDNA detection may guide the optimal endocrine therapy strategy for patients with advanced breast cancer and achieve the benefit of progression free survival. NGS detection might distinguish patients with HER2 mutation and provide new treatment strategies. Clinical trial information: NCT03786575.

A phase II, single-arm, non-randomized study of alpelisib (BYL719) in combination with continued endocrine therapy following progression on endocrine therapy in hormone receptor–positive, HER2-negative, PIK3CA-mutant metastatic breast cancer: A Big Ten Cancer Research Consortium Study (btcrc-BRE19-409).

TPS1114 Background: The PI3K pathway is frequently altered in hormone receptor positive (HR+) breast cancer (BC) and 40% of patients have PIK3CA mutations. The PI3Kα-specific inihibitor, Alpelisib, is FDA-approved in combination with fulvestrant for treatment of patients with HR+ HER2 negative (HER2-) PIK3CA mutated, advanced BC following progression on or after a non-fulvestrant endocrine therapy (ET) based regimen. We hypothesized that the benefit seen in the seminal SOLAR-1 study that compared alpelisib plus fulvestrant to placebo with fulvestrant, was due to the addition of alpelisib, rather than the change to fulvestrant, such that addition of alpelisib to ongoing ET at time of progression could lead to similar outcomes. Unlike SOLAR-1, our study continues prior ET at time of progression and requires prior CDK4/6 inhibitor therapy. Methods: We designed a phase II single arm study that tests the efficacy of adding alpelisib to ongoing ET at time of progression on ET. The primary objective is to estimate the progression–free survival (PFS) of alpelisib with continued ET (aromatase inhibitor or fulvestrant) following progression in patients with HR+ HER2-, PIK3CA mutant advanced BC. Secondary objectives are to estimate overall response rate, clinical benefit rate, duration of response, overall survival and safety/tolerability. Correlative studies include evaluation of PIK3CA activity in circulating tumor cell liquid biopsy at baseline, C1D15, C2D1, C4D1 and at progression and correlation with primary and secondary objectives. Eligibility: Men and postmenopausal female patients with histologically confirmed ER and/or PR ≥1%, HER2- metastatic or unresectable BC with PIK3CA mutation and either measurable disease or at least one predominantly lytic bone lesion. No more than two lines of ET and no chemotherapy in the metastatic setting is allowed and patients must have received treatment with a CDK4/6 inhibitor and have progressed on ET as last line of therapy. Exclusions include prior PIK3CA, mTOR or AKT inhibitors in the metastatic setting, symptomatic active CNS metastases or CNS metastases that require therapeutic interventions. Statistical Analysis. The sample size calculation is based on testing the null hypothesis that the median PFS is at most 5 months against the alternative that the PFS is greater than 5 months (based on data from SOLAR-1). An increase of at least 3 months in the median PFS will be considered a sufficient efficacy signal. A sample size of 44 subjects is required to detect an anticipated increase in the median PFS from 5 to 8 months at the one-sided 0.10 significance level with 90% power, assuming a uniform accrual period of 24 months. Clinical trial information: NCT04762979.

Factors associated with CDK 4/6 inhibitor use for patients with advanced, hormone positive, HER-2-negative breast cancer.

e13038 Background: “CDK4/6 inhibitors have emerged as a standard of care for patients with HR-positive, HER2-negative advanced breast cancer.” Wayne Kuznar ASCO Reading Room 10.29.2019. Within an academic institution there were concerns that CDK 4/6 inhibitors were not utilized as indicated. We conducted an analysis of CDK 4/6 inhibitor use for patients with advanced, hormone positive, HER2 negative breast cancer to assess factors associated with CDK 4/6 inhibitor use. Methods: We conducted a retrospective medical records review of patients treated at an academic medical center from 01/1/2015 to 9/30/2020 with stage IV, hormone positive and HER2 negative breast cancer. We compared characteristics for patients that received one or more CDK 4/6 inhibitors to those who did not receive any CDK 4/6 inhibitors. Statistical analysis used Fishers exact 2-sided test via GraphPad QuickCalcs website. Results: 162 patient records met inclusion criteria, 73% (119/162) received one or more CDK 4/6 inhibitors as part of their care. The average age of patients who received CDK 4/6 inhibitors was 59.9, as compared to 66.9 average age in patients who did not receive CDK 4/6 inhibitors. Patients who received CDK 4/6 inhibitors were more likely to have received chemotherapy (Table, p &lt; 0.0001), have a family history of cancer (p &lt; 0.0001) and have a Charlson comorbidity index of 5 or more (p = 0.0005). Patients receiving CDK 4/6 inhibitors trended more likely to have used tobacco at some point (p = 0.09). Patients who did not receive CDK 4/6 were more likely to have refused, moved or be in hospice (p = 0.003). There were no statistically significant differences based on patient status, timing of diagnosis or timing of first hormone receptor positive dose. Further analysis of the 27% (43/162) of patients not receiving CDK 4/6 inhibitors identified that 40% (17/43) died, 28% (12/43) had Charlson comorbidity score of 7 or more, 19% (8/43) refused treatment. The remaining 14% (6/43), 4% (6/162) of entire population, did not have a clear reason for not getting CDK 4/6 inhibitors, of those 4 received hormone therapy, 1 received chemotherapy and 1 received both. Conclusions: In a retrospective analysis of patient records, we found consistent use of CDK 4/6 inhibitors for indicated patients. Patients who did not receive CDK 4/6 inhibitors died, had a high co-morbidity index, or refused treatment. Only 4% of the population analyzed did not have a visible reason to not receive CDK 4/6 inhibitors.[Table: see text]

Neoadjuvant HER2-targeted therapy +/- immunotherapy with pembrolizumab (neoHIP): An open-label randomized phase II trial.

TPS624 Background: Immune checkpoint inhibition (ICI) is synergistic with HER2-directed therapy in pre-clinical models. Clinically, pembrolizumab (K)-mediated ICI plus HER2-directed therapy with trastuzumab (H) was safe and demonstrated modest activity in H-resistant HER2-positive (HER2+) metastatic breast cancer. Because ICI may confer more robust activity when administered earlier in the course of disease, H and K administered in the curative-intent, treatment-naive setting may allow for de-escalation of cytotoxics; confer life-long, tumor-specific immunity; and ultimately, improve cure rates. Moreover, the synergy of H and K with paclitaxel (T) may overcome the need for dual HER2-blockade with H plus pertuzumab (P). In this randomized, multicenter, phase II, open-label trial the efficacy and safety of neoadjuvant THP vs THP-K vs TH-K are explored. Methods: 174 patients (pts) ≥18y with previously untreated, stage II-III, HER2+ breast cancer will be randomized and stratified by clinical nodal status (positive vs. negative) and hormone receptor status (positive vs. negative). In arm A, pts receive T at 80mg/m2 weekly for 12 weeks, H at 8mg/Kg (loading dose) and then 6mg/Kg every 3 weeks x 3 doses, P at 840 mg (loading dose) and then 420mg/Kg every 3 weeks x 3 doses (THP). In arm B, pts receive THP plus K at 200mg every 3 weeks x 4 doses (THP-K). In arm C, pts receive TH-K. Definitive surgery is 3-6 weeks after the last dose. After surgery, pts are treated per the treating physician’s discretion including radiotherapy per local clinical standard. Pts whose tumors are hormone-receptor positive will receive hormone therapy per local standard-of-care. The primary end point is pathologic complete response (pCR) rate in the breast and axilla (ypT0/Tis ypN0). Secondary end points include pCR rate by ypT0ypN0 and ypT0/Tis, residual cancer burden index, event free survival, breast conserving surgery rate, safety and overall survival. Exploratory correlative studies will characterize potential immune biomarkers predictive of efficacy and/or toxicity. Clinical trial information: NCT03747120.

Use of breast MRI to distinguish treatment failure versus new primary tumor following single fraction breast intraoperative radiotherapy for breast cancer (SF-IORT).

e12534 Background: Single-fraction, intraoperative radiation therapy (SF-IORT) can replace whole breast radiotherapy (WBT) in select patients after lumpectomy for breast cancer. By combining histology review with co-registration of breast MRI at diagnosis and following an in-breast tumor recurrence, we sought to characterize IBTR as: missed on initial MRI, treatment failure, or new primary tumor. This has important implications for both breast MRI and understanding the effectiveness of SF-IORT. Methods: We reviewed our IORT database for patients with IBTR. Three radiologists recorded findings on DCE-MRI, mammograms and ultrasound, pathology at initial diagnosis and IBTR, and time to IBTR. Results: 90 women received SF-IORT between 12/6/2002 - 4/10/2019. There were 6 IBTRs (average age at recurrence 63, range 49-71 years). For these 6 patients, initial diagnostic mammograms showed fatty (1), scattered (4) or extremely dense (1) breasts with suspicious masses (4), calcifications (1), or asymmetry (1), average size 1.4 cm: range 0.3 - 2.0 cm. On MRI, background parenchymal enhancement was minimal (2), mild (2), moderate (1), or marked (1), showing a mass (4), mass/distortion (1), or post-biopsy marker/no abnormal enhancement (1). Initial pathology showed 2 IDC, 3 IDC/DCIS, and 1 DCIS, (average size 1.7 cm, range 1.1 - 2.4 cm) with 6/6 ER +, 5/6 PR + and 6 HER2 negative. IDC Ki-67 ranged from 5-25%. 5/6 patients had sentinel lymph node biopsy (SLNB) with 1/5 having a positive SLN. 4/6 received endocrine therapy. One patient declined follow-up mammography. After IORT, IBTR (average size 1.4 cm, range 0.7 - 3.6 cm) was diagnosed by mammography (3), palpable breast lump (2), or palpable axillary lymph node (LN) (1) shown as mass (4), mass/calcifications (1), or abnormal LN (1). IBTR occurred post-SF-IORT an average of 141.7 months, range 88.3 to 195.8 months. 2/6 IBTR occurred near the biopsy cavity. Subsequent surgery included mastectomy (3), re-excision lumpectomy/RT (2), or axillary LN dissection/RT (1) showing 4 IDC, 1 IDC/DCIS, and 1 IDC /ILC (6/6 ER +; 3/6 PR positive; 2 PR weakly positive; and 5 HER2 negative, 1 HER2 equivocal). Ki-67 ranged from 1-70%. Conclusions: 6/90 (6.6%) patients had an IBTR an average of 141.7 months post SF-IORT with 2/6 near the biopsy cavity. Breast MRI reliably screens patients for SF-IORT. Co-registration of imaging can help distinguish true recurrences from new primary tumors.

The correlation analysis of 21-gene assay use in uninsured and underrepresented minorities with estrogen receptor (ER) positive HER2 negative breast cancer.

e12531 Background: 21-gene breast cancer recurrence-score assay (Oncotype DX) have been used to predict recurrence risks and guide adjuvant chemotherapy. However, access to such tests is limited, especially in a population concentrated with uninsured and underserved patient populations. Previously equations such as the Magee equation has been proposed to predict correlation of the recurrence score and the estimated recurrence score with high concordance rate. This study examines the concordance of such an assay to predicted scores in uninsured and underrepresented minority heavy public hospital. Methods: We performed a retrospective chart review of 68 women with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer seen at University Hospital (public safety net hospital in Newark, New Jersey with greater majority of the patient population consists of underrepresented minorities such as Black/African Americans and Latino/Hispanics). 6 patients did not have pathology records, 9 patients did not have the Oncotype information available, and 4 patients were waiting on the results. Of the pre-menopausal eligible patients, two did not have any treatment or follow up information available and were included as part of the correlation assay, however, no. Results: Of the 47 eligible patients with follow-up information, 13 had a low recurrence score of up to 10 if post-menopausal and up to 15 if pre-menopausal, 22 had an intermediate recurrence score of 11 to 25 if post-menopausal and 16 to 25 if pre-menopausal, and 12 had a high recurrence score of greater than 26 according to the national comprehensive cancer network guidelines. The Pearson correlation between the Magee predicted score and Oncotype recurrence score was 0.73 (p &lt; 0.001). All patients received hormone therapy and 5 patients total had recurred. 2 were pre-menopausal and had received adjuvant chemotherapy. 3 were post-menopausal in low and intermediate categories who had not received adjuvant chemotherapy. Conclusions: This study shows a high correlation between the predicted Magee score and Oncotype recurrence score. This reflects a possible use in the prediction scoring system as another resource for prognostication and guidance in treatment especially in the underinsured population.

Improving outcomes for women aged 70 years or above with early breast cancer: research programme including a cluster RCT

Improving outcomes for women aged 70 years or above with early breast cancer: research programme including a cluster RCT

ARV-471, an estrogen receptor (ER) PROTACdegrader, combined with palbociclib in advanced ER+/human epidermal growth factor receptor 2–negative (HER2-) breast cancer: Phase 1b cohort (part C) of a phase 1/2 study.

TPS1120 Background: ARV-471 is a novel, potent, orally bioavailable PROteolysis TArgeting Chimera (PROTAC) protein degrader that selectively targets the ER. In xenograft models, ARV-471 demonstrated substantially greater ER degradation and antitumor activity compared with the selective ER degrader fulvestrant. In the phase 1 dose escalation portion (Part A) of the first-in-human phase 1/2 study, ARV-471 monotherapy was well tolerated and showed antitumor activity in patients with ER+/HER2- locally advanced or metastatic breast cancer who had previously received endocrine therapy and a cyclin-dependent kinase (CDK)4/6 inhibitor; the clinical benefit rate (rate of confirmed complete or partial response or stable disease ≥24 weeks) was 40% (95% CI: 26%–56%) in 47 evaluable patients. The phase 2 VERITAC expansion cohort (Part B) is further evaluating ARV-471 monotherapy in this patient population. Palbociclib, a CDK4/6 inhibitor, plus fulvestrant is a standard treatment option for patients with ER+/HER2- breast cancer who have had disease progression on endocrine therapy. ARV-471 plus palbociclib resulted in substantially greater tumor growth inhibition in xenograft models compared with palbociclib plus fulvestrant, supporting further investigation of the ARV-471 plus palbociclib combination in patients with ER+ breast cancer. Here we describe Part C of the phase 1/2 study, which evaluates the safety and clinical activity of ARV-471 plus palbociclib in patients with breast cancer who previously received endocrine therapy. Methods: Eligible patients (aged ≥18 years) have histologically or cytologically confirmed ER+/HER2- advanced breast cancer and have received ≥1 prior endocrine therapy and ≤2 prior chemotherapy regimens for advanced disease; prior CDK4/6 inhibitor therapy is permitted. Patients with known symptomatic brain metastases requiring steroids are excluded. ARV-471 and palbociclib will be administered orally once daily in 28-day cycles; ARV-471 will be given continuously and palbociclib for 21 days followed by 7 days off treatment. Primary objectives are to evaluate the safety and tolerability of ARV-471 plus palbociclib and select the recommended phase 2 dose and schedule of the combination (based on the incidence of dose-limiting toxicities during the first cycle and the frequency and severity of adverse events and laboratory abnormalities). Secondary objectives are to assess preliminary antitumor activity of ARV-471 plus palbociclib (based on overall response rate per Response Evaluation Criteria in Solid Tumors v1.1, clinical benefit rate, progression-free survival, and duration of response) and pharmacokinetic parameters. Clinical trial information: NCT04072952.

Does hormonal therapy improve sperm retrieval rates in men with non-obstructive azoospermia: a systematic review and meta-analysis.

The beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either normal gonadotrophins or hypergonadotropic hypogonadism prior to surgical sperm retrieval (SSR) is controversial. Although the European Association of Urology guidelines state that hormone stimulation is not recommended in routine clinical practice, a significant number of patients undergo empiric therapy prior to SSR. The success rate for SSR from microdissection testicular sperm extraction is only 40-60%, thus hormonal therapy could prove to be an effective adjunctive therapy to increase SSR rates. The primary aim of this systematic review and meta-analysis was to compare the SSR rates in men with NOA (excluding those with hypogonadotropic hypogonadism) receiving hormone therapy compared to placebo or no treatment. The secondary objective was to compare the effects of hormonal therapy in normogonadotropic and hypergonadotropic NOA men. A literature search was performed using the Medline, Embase, Web of Science and Clinicaltrials.gov databases from 01 January 1946 to 17 September 2020. We included all studies where hormone status was confirmed. We excluded non-English language and animal studies. Heterogeneity was calculated using I2 statistics and risk of bias was assessed using Cochrane tools. We performed a meta-analysis on all the eligible controlled trials to determine whether hormone stimulation (irrespective of class) improved SSR rates and also whether this was affected by baseline hormone status (hypergonadotropic versus normogonadotropic NOA men). Sensitivity analyses were performed when indicated. A total of 3846 studies were screened and 22 studies were included with 1706 participants. A higher SSR rate in subjects pre-treated with hormonal therapy was observed (odds ratio (OR) 1.96, 95% CI: 1.08-3.56, P = 0.03) and this trend persisted when excluding a study containing only men with Klinefelter syndrome (OR 1.90, 95% CI: 1.03-3.51, P = 0.04). However, the subgroup analysis of baseline hormone status demonstrated a significant improvement only in normogonadotropic men (OR 2.13, 95% CI: 1.10-4.14, P = 0.02) and not in hypergonadotropic patients (OR 1.73, 95% CI: 0.44-6.77, P = 0.43). The literature was at moderate or severe risk of bias. This meta-analysis demonstrates that hormone therapy is not associated with improved SSR rates in hypergonadotropic hypogonadism. While hormone therapy improved SSR rates in eugonadal men with NOA, the quality of evidence was low with a moderate to high risk of bias. Therefore, hormone therapy should not be routinely used in men with NOA prior to SSR and large scale, prospective randomized controlled trials are needed to validate the meta-analysis findings.

247P Usage and side effects of each common aromatase inhibitor in 5 large European countries: Real-world data analysis

Hormonal treatment (HT) is a common and effective therapy in hormone receptor (HR)-positive breast cancer patients, either metastatic or non-metastatic. Aromatase Inhibitors (AIs) are considered the most effective HT in postmenopausal women. Commonly used AIs (letrozole, anastrozole, exemestane) may cause various side effects. This Real World Data analysis aimed to compare AI usage frequency and side effect incidence among European patients.

Management and prognosis comparison between incidental and nonincidental intravenous leiomyomatosis: a retrospective single-center real-life experience.

BackgroundIntravenous leiomyomatosis (IVL) is a rare, difficult-to-treat type of smooth muscle tumor that originates from the uterine myoma. However, its clinical characteristics, management, and prognosis are not clearly understood. Moreover, the 2 different methods used to diagnose IVL—incidental and nonincidental—result in completely different treatments.MethodsWe conducted a single-center, retrospective study. Our real-life case series included patients pathologically diagnosed with IVL between July 2011 and December 2020. All patients with IVL were divided into 2 groups: an incidental group and a nonincidental group. Medical records of patients, including clinical characteristics, primary treatment, treatment after recurrence, and prognosis, were reviewed.ResultsA total of 39 patients were included in the study, with a median patient age of 47 years. Of the 39 cases, 15 (38.5%) were incidentally diagnosed with only intrapelvic tumors. Among the 24 patients with IVL in the nonincidental group, tumor spread in the inferior vena cava, right heart, and pulmonary artery was identified in 4, 17, and 3 patients, respectively. The most common symptoms were abnormal uterine bleeding in the incidental group and chest distress and dyspnea in the nonincidental group. Among the 15 patients in the incidental group, ovary-preserving surgery was performed in 6 young women (≤40 years old), of whom 3 underwent myomectomy. All 24 patients with IVL in the nonincidental group underwent thrombectomy without uterine or ovary preservation by multidisciplinary surgical treatment. Only 1 patient in each group underwent postoperative adjuvant therapy. During the median follow-up of 36.0 months, recurrence was recorded in 5 (12.8%) cases in the incidental group, with no deaths recorded. Only 1 patient was lost to follow-up. No recurrence was noted in the cases in the nonincidental group. Among the 5 patients who experienced recurrence, 4 received secondary surgical treatment and 1 received hormone therapy. All patients were alive as of this report.ConclusionsPatients with IVL who are diagnosed incidentally have a higher recurrence risk than those who are diagnosed nonincidentally and undergo complete tumor resection. However, patients incidentally diagnosed with IVL can still experience long disease-free survival rates following secondary surgical treatment after recurrence.

Real-World Treatment for Menopausal Symptoms in the U.S. by Practitioner Type [A133

INTRODUCTION: Vasomotor symptoms are the most common menopausal symptoms for which women seek treatment. We describe current treatment use by practitioner type (gynecologists versus primary care providers [PCPs]) and U.S. geographic region. METHODS: This subgroup analysis of a noninterventional, observational study used a convenience sample of 283 practitioners (131 gynecologists, 152 PCPs) who abstracted data on menopause-specific therapy from medical records of women aged 40‒60 years who initially presented with menopausal symptoms between January 1, 2016, and December 31, 2019. Data were summarized descriptively. RESULTS: Practitioners provided data for 1,016 women (from gynecologists: 512; PCPs: 504). About half the women overall experienced symptoms for ≥6 months before consultation. Patients of gynecologists had more vaginal and sexual symptoms recorded than patients of PCPs. Gynecologists’ patients more commonly had prescription medications (63% versus 57%) but less commonly had nonprescription therapies/interventions (59% versus 66%) documented than PCPs’ patients. They more often received hormone therapy (HT; 76% versus 64% of patients with any prescription) and compounded HT (17% versus 7%) and less often received selective serotonin reuptake inhibitors (SSRIs; 11% versus 19%) and serotonin-norepinephrine reuptake inhibitors (2% versus 12%) than PCPs’ patients. Black cohosh was the most frequently documented nonprescription therapy by gynecologists (24%) and PCPs (35%); gynecologists more commonly documented Estroven (16% versus 10%). Compounded HT use was more common in the U.S. Southeast and Southwest (∼20%), and SSRI use was more common in the Northeast (22%) than other regions. CONCLUSION: Prescribing patterns for menopausal symptoms vary by practitioner type and U.S. region.