Positive Estrogen Receptor Status Research Articles

Landscape of HER2-low breast cancer: Insights from a six-year study on incidence and clinicopathological characteristics.

e13148 Background: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has emerged as a subtype of breast cancer, defined by HER2 1+ or 2+ in immunohistochemistry (IHC) and the absence of the ERBB2 gene amplification on fluorescence in situ hybridization (FISH). Recent trials showed marked response of HER2 breast cancer to novel anti-HER2 antibody-drug conjugates, rising interest in the HER2-low subtype. To date, data on characteristics of HER2-low breast cancer subtype is limited. Herein, we describe the clinicopathological characteristics of HER2-low breast cancer subtype compared HER2-zero/negative breast cancer. Methods: Real-world data from the Anatomic Pathology Division of Hotel Dieu de France, spanning 2017-2022, was retrospectively collected. Patients with HER2-IHC 3+ and HER2-IHC 2+ with ISH-amplified (HER2-positive) were excluded to compare HER2-low to HER2-zero breast cancer subtypes. Patients were then categorized based on their hormone receptor (HR) status. Clinicopathological characteristics between the groups were compared using a Chi-Square and Mann–Whitney U tests. Results: Out of 1195 patients, we observed 341 (28.5%) HER2-low breast cancers cases. HER2-positive breast cancer cases (n=178; 14.9%) were subsequently excluded. There was no significant difference in age and sex between the HER2-low and the HER2-zero group (p=0.3 and 0.8, respectively). HER2-low breast cancer was associated with positive estrogen receptor (ER) status and positive progesterone receptor (PR) status (p<0.001 and p=0.01, respectively). Ductal adenocarcinomas were more frequently observed in the HER2-low group, whereas lobular and metaplastic adenocarcinomas were especially prevalent in the HER2-zero group (all p<0.001). When stratified by HR status, 87.4% of patients had HR-positive status and 12.6% were HR-negative. Furthermore, the occurrence rate of tumors with a low Ki-67 labeling index was comparable between the two groups (p=0.9). However, among the HR-negative group, HER2-low tumors tended to show lower proliferation index compared to HER2-zero tumors (p = 0.04; Table). Conclusions: In conclusion, this study showed that HER2-low is a distinct from HER2-zero and is frequently present among patients with breast cancer. Clinicopathological features such as histological type differ between HER2-zero and HER2-low breast cancer. Our findings suggest that, within HR-negative breast cancer, breast cancer with low HER2 expression exhibits a less aggressive profile when compared to HER2-zero tumors. [Table: see text]

Prognostic Factors Associated with Breast Cancer-Specific Survival from 1995 to 2022: A Systematic Review and Meta-Analysis of 1,386,663 Cases from 30 Countries.

Breast cancer is the fifth-ranked cancer globally. Despite early diagnosis and advances in treatment, breast cancer mortality is increasing. This meta-analysis aims to examine all possible prognostic factors that improve/deteriorate breast cancer-specific survival. MEDLINE, PubMed, ScienceDirect, Ovid, and Google Scholar were systematically searched until September 16, 2023. The retrieved studies from 1995 to 2022 accumulated 1,386,663 cases from 30 countries. A total of 13 out of 22 prognostic factors were significantly associated with breast cancer-specific survival. A random-effects model provided a pooled estimate of the top five poorest prognostic factors, including Stage 4 (HR = 12.12; 95% CI: 5.70, 25.76), followed by Stage 3 (HR = 3.42, 95% CI: 2.51, 4.67), a comorbidity index ≥ 3 (HR = 3.29; 95% CI: 4.52, 7.35), the poor differentiation of cancer cell histology (HR = 2.43; 95% CI: 1.79, 3.30), and undifferentiated cancer cell histology (HR = 2.24; 95% CI: 1.66, 3.01). Other survival-reducing factors include positive nodes, age, race, HER2-receptor positivity, and overweight/obesity. The top five best prognostic factors include different types of mastectomies and breast-conserving therapies (HR = 0.56; 95% CI: 0.44, 0.70), medullary histology (HR = 0.62; 95% CI: 0.53, 0.72), higher education (HR = 0.72; 95% CI: 0.68, 0.77), and a positive estrogen receptor status (HR = 0.78; 95% CI: 0.65, 0.94). Heterogeneity was observed in most studies. Data from developing countries are still scarce.

Landscape of HER2-low breast cancer: Insights from a six-year study on prevalence and clinicopathological characteristics

Human epidermal growth factor receptor 2 (HER2)-low breast cancer has emerged as a subtype of breast cancer, defined by HER2 1+/2+ in immunohistochemistry (IHC) and absence of ERBB2 gene amplification on fluorescence in situ hybridization (FISH). Recent trials showed marked response of HER2-low breast cancer to novel anti-HER2 antibody-drug-conjugates. Data on characteristics of HER2-low breast cancer subtype is limited. Real-world data from the Anatomic Pathology Department of Hotel-Dieu de France, spanning 2017–2023, was retrospectively collected. HER2-positive patients were excluded to compare HER2-low to HER2-zero breast cancer subtypes. Clinicopathological characteristics between the groups were compared using a Chi-Squared test. Out of 1195 patients, we observed 341 (28.5 %) HER2-low breast cancers cases. HER2-positive breast cancer cases (n = 178; 14.9 %) were excluded. There was no significant difference in age and sex between HER2-low and HER2-zero group (p = 0.33 and 0.79, respectively). HER2-low breast cancer was associated with positive estrogen receptor status and positive progesterone receptor status (p < 0.001 and p = 0.01, respectively). Ductal adenocarcinomas were more commonly observed in HER2-low group (p < 0.001). When stratified by hormone (HR) status, 87.4 % of patients had HR-positive status and 12.6 % were HR-negative. Among the HR-negative group, HER2-low tumors tended to show lower proliferation index compared to HER2-zero tumors (25%vs.10 %, p = 0.04). This study showed that HER2-low is distinct from HER2-zero and is common among patients with breast cancer. Clinicopathological features such as histological type differ between HER2-zero and HER2-low breast cancer. Within HR-negative breast cancer, those with low HER2 expression exhibit a less aggressive profile compared to HER2-zero tumors.

A new prediction nomogram of non-sentinel lymph node metastasis in cT1-2 breast cancer patients with positive sentinel lymph nodes

We aimed to analyze the risk factors and construct a new nomogram to predict non-sentinel lymph node (NSLN) metastasis for cT1-2 breast cancer patients with positivity after sentinel lymph node biopsy (SLNB). A total of 830 breast cancer patients who underwent surgery between 2016 and 2021 at multi-center were included in the retrospective analysis. Patients were divided into training (n = 410), internal validation (n = 298), and external validation cohorts (n = 122) based on periods and centers. A nomogram-based prediction model for the risk of NSLN metastasis was constructed by incorporating independent predictors of NSLN metastasis identified through univariate and multivariate logistic regression analyses in the training cohort and then validated by validation cohorts. The multivariate logistic regression analysis revealed that the number of positive sentinel lymph nodes (SLNs) (P < 0.001), the proportion of positive SLNs (P = 0.029), lymph-vascular invasion (P = 0.029), perineural invasion (P = 0.023), and estrogen receptor (ER) status (P = 0.034) were independent risk factors for NSLN metastasis. The area under the receiver operating characteristics curve (AUC) value of this model was 0.730 (95% CI 0.676–0.785) for the training, 0.701 (95% CI 0.630–0.773) for internal validation, and 0.813 (95% CI 0.734–0.891) for external validation cohorts. Decision curve analysis also showed that the model could be effectively applied in clinical practice. The proposed nomogram estimated the likelihood of positive NSLNs and assisted the surgeon in deciding whether to perform further axillary lymph node dissection (ALND) and avoid non-essential ALND as well as postoperative complications.

Radiotherapy versus low-dose tamoxifen following breast-conserving surgery for low-risk and estrogen receptor-positive breast ductal carcinoma in situ: an international open-label randomized non-inferiority trial (TBCC-ARO DCIS Trial)

BackgroundRadiotherapy (RT) following breast-conserving surgery (BCS) is mainly used to decrease the rate of ipsilateral breast tumor recurrence (IBTR) in women with breast ductal carcinoma in situ (DCIS). Recent studies have demonstrated that low-dose tamoxifen significantly reduces IBTR in breast DCIS. Here, we aim to determine whether the administration of low-dose tamoxifen is non-inferior to RT in preventing IBTR in patients with low-risk characteristics of breast DCIS.Methods/designThis is a prospective, international, open-label, randomized, non-inferiority trial. Patients with low-risk clinicopathologic features (> 40 years old, low risk of breast cancer susceptibility gene (BRCA) 1 and BRCA2 mutations, mammographically detected unicentric and non-mass lesions, low- or intermediate-grade without comedo or necrosis, measuring < 2.5 cm with margins ≥ 3 mm, and estrogen receptor-positive status) of DCIS who underwent BCS will be randomized at a 1:1 ratio to either receive tamoxifen (5 mg/day) for 5 years or undergo RT with conventional fractions (50 Gy in 25 fractions) or hypofractionations (40.05 Gy in 15 fractions). Randomization will be stratified by the Taiwan Breast Cancer Consortium. As approximately 5% of patients cannot tolerate the side effects of low-dose tamoxifen and will receive RT, we estimate that 405 patients will be randomized to a low-dose tamoxifen arm and 405 patients to the RT arm, according to a non-inferiority margin within 5% of IBTR difference and 90% β-power noticing non-inferiority. The primary endpoints are breast tumor recurrence, including ipsilateral, regional, contralateral, and distant recurrence of breast DCIS or invasive cancer. The secondary endpoints are overall survival and adverse effects of RT and tamoxifen. Translational studies will also be conducted for this trial.DiscussionThis is the first non-inferiority trial on breast DCIS. This study will provide an important recommendation for clinical physicians on whether to use low-dose adjuvant tamoxifen for patients with low-risk breast DCIS who do not want to receive adjuvant RT.Trial registrationClinicalTrials.gov, ID: NCT04046159, Registered on April 30, 2019.

Safety of Vaginal Estrogen Therapy for Genitourinary Syndrome of Menopause in Women With a History of Breast Cancer.

To assess the risk of recurrence of breast cancer associated with vaginal estrogen therapy in women diagnosed with genitourinary syndrome of menopause with a history of breast cancer using a large U.S. claims database. A U.S. health research network (TriNetX Diamond Network) was queried from January 2009 to June 2022. Our cohort consisted of women diagnosed with breast cancer within 5 years before the initial genitourinary syndrome of menopause diagnosis. Patients with active disease , defined as those undergoing mastectomy, radiation treatment, or chemotherapy within 3 months before diagnosis of genitourinary syndrome of menopause, were excluded. Recurrence was defined as mastectomy, radiation, chemotherapy, or secondary malignancy within 3 months to 5 years after the initiation of vaginal estrogen therapy for genitourinary syndrome of menopause. The study cohort included those with three or more vaginal estrogen prescriptions. The control cohort included women with breast cancer without any vaginal estrogen prescriptions after genitourinary syndrome of menopause diagnosis. Propensity matching was performed. A subanalysis by positive estrogen receptor status, when available, was performed. We identified 42,113 women with a diagnosis of genitourinary syndrome of menopause after breast cancer diagnosis with any estrogen receptor status, 5.0% of whom received vaginal estrogen. Of the initial cohort, 10,584 patients had a history of positive estrogen receptor breast cancer, and 3.9% of this group received vaginal estrogen. Risk of breast cancer recurrence was comparable between those who received vaginal estrogen and those who did not in both the any estrogen receptor (risk ratio 1.03, 95% CI 0.91-1.18) and positive estrogen receptor (risk ratio 0.94, 95% CI 0.77-1.15) status analyses. In a large, claims-based analysis, we did not find an increased risk of breast cancer recurrence within 5 years in women with a personal history of breast cancer who were using vaginal estrogen for genitourinary syndrome of menopause.

(007) The Safety of Vaginal Estrogen Therapy for Genitourinary Syndrome of Menopause in Women with a History of Breast Cancer – A Claims Database Analysis

Abstract Introduction Systemic treatment for breast cancer (BC) may result in genitourinary syndrome of menopause (GSM) in up to 70% of postmenopausal BC survivors. Though systemic estrogen therapy is usually avoided in these patients, vaginal estrogen therapy may be prescribed to treat GSM symptoms. However, few eligible patients with GSM and history of BC are prescribed vaginal estrogen due to concern for cancer recurrence. Objective Our objective was to assess the recurrence rates of BC by vaginal estrogen therapy status in women diagnosed with GSM with a history of BC using a large US claims database. Methods A US health research network (the TriNetX Diamond Network) of over 200 million patients was queried from 2009 to 2022. Females with a diagnosis of BC (C50, Z86.000) within the five years before an initial GSM diagnosis (ICD-10 N90.5, N95.2) were included. Patients who underwent mastectomy (1015054), radiation oncology treatment (1010843), and/or chemotherapy (1002) within three months prior to the diagnosis of GSM were excluded as they were considered to have active disease. Recurrence was defined as the need for mastectomy, radiation, or chemotherapy within three months to five years after initiating vaginal estrogen therapy for GSM. We excluded women diagnosed with cancers other than BC in the 5 years prior to or after their initial GSM diagnosis. The study cohort included those with ≥3 vaginal estrogen (GU500) prescriptions, while the control cohort only included women without vaginal estrogen prescriptions. Propensity-matching between the cohorts for age, ethnicity, race, family history of breast neoplasm (Z80.3), overweight and obesity (E66), hormone replacement therapy (Z79.890), and tobacco usage (Z72.0) was conducted. A sub-analysis by positive estrogen receptor (+ER) status (Z17.0), when available, was performed. Results Amongst females with GSM following a history of BC, 2,113 (5%) received ≥3 vaginal estrogen prescriptions, while 40,019 patients (95%) didn’t receive any vaginal estrogen prescriptions. Amongst those with a +ER status, 410 females (3.9%) received ≥3 vaginal estrogen prescriptions, while 10,182 (96.1%) didn’t receive any vaginal estrogen prescriptions. Compared to matched controls, females with ≥3 vaginal estrogen prescriptions (n=2,111) had similar risks of mastectomy procedures (relative risk (RR) 1.06 [95% CI 0.54, 2.06]), chemotherapy (RR 1.16 [0.98, 1.37]), and radiation treatment (RR 1.06 [0.54, 2.11]) within three months to five years following the first estrogen prescription (Table 1). Individuals with a +ER status and ≥3 vaginal estrogen prescriptions (n=409) had a similar risk of mastectomy procedures, chemotherapy, or radiation treatment (RR 1.07 [0.86, 1.33]) within three months to five years following the first prescription compared to matched controls (Table 1). Conclusions In this large claims-based analysis, we found similar risks of mastectomy, chemotherapy, and radiation treatment, which serve as proxies for recurrence, after the use of vaginal estrogen for GSM in women with a personal history of BC within the five years prior to their GSM diagnosis. These results suggest that vaginal estrogen therapy in women with GSM and history of BC is not associated with an increased risk of BC recurrence and may hence be safe. Disclosure No

A machine learning-Based model to predict early death among bone metastatic breast cancer patients: A large cohort of 16,189 patients.

Purpose: This study aims to develop a prediction model to categorize the risk of early death among breast cancer patients with bone metastases using machine learning models. Methods: This study examined 16,189 bone metastatic breast cancer patients between 2010 and 2019 from a large oncological database in the United States. The patients were divided into two groups at random in a 90:10 ratio. The majority of patients (n = 14,582, 90%) were served as the training group to train and optimize prediction models, whereas patients in the validation group (n = 1,607, 10%) were utilized to validate the prediction models. Four models were introduced in the study: the logistic regression model, gradient boosting tree model, decision tree model, and random forest model. Results: Early death accounted for 17.4% of all included patients. Multivariate analysis demonstrated that older age; a separated, divorced, or widowed marital status; nonmetropolitan counties; brain metastasis; liver metastasis; lung metastasis; and histologic type of unspecified neoplasms were significantly associated with more early death, whereas a lower grade, a positive estrogen receptor (ER) status, cancer-directed surgery, radiation, and chemotherapy were significantly the protective factors. For the purpose of developing prediction models, the 12 variables were used. Among all the four models, the gradient boosting tree had the greatest AUC [0.829, 95% confident interval (CI): 0.802-0.856], and the random forest (0.828, 95% CI: 0.801-0.855) and logistic regression (0.819, 95% CI: 0.791-0.847) models came in second and third, respectively. The discrimination slopes for the three models were 0.258, 0.223, and 0.240, respectively, and the corresponding accuracy rates were 0.801, 0.770, and 0.762, respectively. The Brier score of gradient boosting tree was the lowest (0.109), followed by the random forest (0.111) and logistic regression (0.112) models. Risk stratification showed that patients in the high-risk group (46.31%) had a greater six-fold chance of early death than those in the low-risk group (7.50%). Conclusion: The gradient boosting tree model demonstrates promising performance with favorable discrimination and calibration in the study, and this model can stratify the risk probability of early death among bone metastatic breast cancer patients.

Peripheral mRNA Expression and Prognostic Significance of Emotional Stress Biomarkers in Metastatic Breast Cancer Patients.

Emotional stress is believed to be associated with increased tumor progression. Stress-induced epigenetic modifications can contribute to the severity of disease and poor prognosis in cancer patients. The current study aimed to investigate the expression profiles along with the prognostic significance of psychological stress-related genes in metastatic breast cancer patients, to rationalize the molecular link between emotional stress and cancer progression. We profiled the expression of selected stress-associated genes (5-HTT, NR3C1, OXTR, and FKBP5) in breast cancer including the stress evaluation of all participants using the Questionnaire on Distress in Cancer Patients-short form (QSC-R10). A survival database, the Kaplan-Meier Plotter, was used to explore the prognostic significance of these genes in breast cancer. Our results showed relatively low expressions of 5-HTT (p = 0.02) and OXTR (p = 0.0387) in metastatic breast cancer patients as compared to the non-metastatic group of patients. The expression of NR3C1 was low in tumor grade III as compared to grade II (p = 0.04). Additionally, the expression of NR3C1 was significantly higher in patients with positive estrogen receptor status. However, no significant difference was found regarding FKBP5 expression in breast cancer. The results suggest a potential implication of these genes in breast cancer pathology and prognosis.

Is repeat breast conservation possible for small ipsilateral breast cancer recurrence?

Most cases of ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) involve small tumors. Although a few guidelines recommend mastectomy, several patients prefer repeat BCS (re-BCS). This study aimed to compare re-BCS and mastectomy in terms of prognosis in patients with IBTR and to identify candidates for re-BCS. The data of patients with small IBTR between 1999 and 2015 were obtained from the Surveillance, Epidemiology, and End Results database. The outcomes of interest were overall survival (OS) and breast cancer-specific survival (BCSS). Multivariable Cox proportional hazards regression models and propensity score matching were applied. Of the 3648 patients with IBTR, 2831 (77.6%) underwent mastectomy and 817 (22.4%) underwent re-BCS. The multivariate Cox model showed that re-BCS was associated with a worse OS (hazard ratio [HR], 1.342; 95% confidence interval [CI], 1.084-1.663) and BCSS (HR, 1.454; 95% CI, 1.004-2.105) compared with mastectomy. The omission of radiation after re-BCS was associated with worse survival overall and especially in patients with estrogen receptor (ER)-negative IBTR (HR, 1.384; 95% CI, 1.110-1.724; and HR, 1.577; 95% CI, 1.075-2.314, respectively). No statistically significant differences were observed in the OS and BCSS between re-BCS with radiation and mastectomy. Subgroup analysis indicated that the surgical approach was not an independent factor for survival in the ER-positive patients with IBTR. Re-BCS should be considered with caution in patients with small IBTR. However, a positive ER status can be an important factor for choosing re-BCS, and radiation therapy may improve oncological safety after re-BCS. Repeat breast-conserving surgery (re-BCS) was investigated to determine if it is safe for patients with small ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS). This population-based cohort study included 2831 patients with small IBTR. Re-BCS was associated with a worse overall survival and breast cancer-specific survival compared with mastectomy. Further analysis found that the IBTR estrogen receptor status was an important basis for choosing re-BCS, and radiation may improve oncological safety after re-BCS.

Vaginal Estrogen Therapy for Vulvovaginal Atrophy in Women with a Personal History of Breast Cancer – A Claims Database Analysis

ABSTRACT Introduction Systemic therapies for breast cancer – selective estrogen receptor modulators (SERM), aromatase inhibitors (AI), oophorectomy, and chemotherapies – often result in vulvovaginal atrophy (VVA or atrophic vaginitis), in up to 70% of postmenopausal breast cancer survivors. While systemic estrogen therapy is often avoided in these patients, vaginal estrogen therapy is a safe treatment option that can be used to treat VVA symptoms in breast cancer survivors. Objective Our objective is to assess the use of vaginal estrogen for women with a diagnosis of VVA and a personal history of breast cancer using a large US claims database. Methods The TriNetX Diamond network database was queried: a US health research network of 190 million patients, encompassing healthcare encounters and prescriptions between 2009-2021. Females with a diagnosis of postmenopausal atrophic vaginitis or atrophy of the vulva (ICD-10 N95.2, N90.5) were included. Of these, women with breast cancer (C50 or Z86.000) were included if the diagnosis was at least 1 month prior to VVA diagnosis. Estrogen receptor status was collected when available (ICD-10 Z17.0, Z17.1). Prescriptions for treatment of VVA were included if prescribed within 1 year of VVA diagnosis. Incidence of vaginal estrogen use in patients with a history of breast cancer was determined for 2013-2015, 2016-2018, and 2019 to present. Results A total of 2,159,766 women with VVA were identified; of whom, 4.8% (n=104,327) had a personal history of breast cancer.Vaginal estrogen prescriptions were less frequent prescribed to women with history of breast cancer compared to women without (11% vs 22%, p&amp;lt;0.01, Table 1). Incidence rate of vaginal estrogen prescriptions for women with VVA and history of breast cancer remained stable around 10-11% from 2013 to present. 25,410 women with VVA and history of breast cancer had positive estrogen receptor status (ER+) and 4,893 had negative estrogen receptor status (ER-). There was no difference in vaginal estrogen prescribing between ER+ and ER- patients (7.4% vs 8.4%). Conclusions While vaginal estrogen can be safely used in women with VVA and personal history of breast cancer, it is prescribed for few eligible patients. Barriers to prescribing and using vaginal estrogen in this population should be explored, in order to significantly improve quality of life for those living with vulvovaginal atrophy. Disclosure No

Fertility preservation for women with breast cancer: a multicentre randomized controlled trial on various ovarian stimulation protocols.

Does ovarian stimulation with the addition of tamoxifen or letrozole affect the number of cumulus-oocyte complexes (COCs) retrieved compared to standard ovarian stimulation in women with breast cancer who undergo fertility preservation? Alternative ovarian stimulation protocols with tamoxifen or letrozole did not affect the number of COCs retrieved at follicle aspiration in women with breast cancer. Alternative ovarian stimulation protocols have been introduced for women with breast cancer who opt for fertility preservation by means of banking of oocytes or embryos. How these ovarian stimulation protocols compare to standard ovarian stimulation in terms of COC yield is unknown. This multicentre, open-label randomized controlled superiority trial was carried out in 10 hospitals in the Netherlands and 1 hospital in Belgium between January 2014 and December 2018. We randomly assigned women with breast cancer, aged 18-43 years, who opted for banking of oocytes or embryos to one of three study arms; ovarian stimulation plus tamoxifen, ovarian stimulation plus letrozole or standard ovarian stimulation. Standard ovarian stimulation included GnRH antagonist, recombinant FSH and GnRH agonist trigger. Randomization was performed with a web-based system in a 1:1:1 ratio, stratified for oral contraception usage at start of ovarian stimulation, positive estrogen receptor (ER) status and positive lymph nodes. Patients and caregivers were not blinded to the assigned treatment. The primary outcome was number of COCs retrieved at follicle aspiration. During the study period, 162 women were randomly assigned to one of three interventions. Fifty-four underwent ovarian stimulation plus tamoxifen, 53 ovarian stimulation plus letrozole and 55 standard ovarian stimulation. Analysis was according to intention-to-treat principle. No differences among groups were observed in the mean (±SD) number of COCs retrieved: 12.5 (10.4) after ovarian stimulation plus tamoxifen, 14.2 (9.4) after ovarian stimulation plus letrozole and 13.6 (11.6) after standard ovarian stimulation (mean difference -1.13, 95% CI -5.70 to 3.43 for tamoxifen versus standard ovarian stimulation and 0.58, 95% CI -4.03 to 5.20 for letrozole versus standard ovarian stimulation). After adjusting for oral contraception usage at the start of ovarian stimulation, positive ER status and positive lymph nodes, the mean difference was -1.11 (95% CI -5.58 to 3.35) after ovarian stimulation plus tamoxifen versus standard ovarian stimulation and 0.30 (95% CI -4.19 to 4.78) after ovarian stimulation plus letrozole versus standard ovarian stimulation. There were also no differences in the number of oocytes or embryos banked. There was one serious adverse event after standard ovarian stimulation: one woman was admitted to the hospital because of ovarian hyperstimulation syndrome. The available literature on which we based our hypothesis, power analysis and sample size calculation was scarce and studies were of low quality. Our study did not have sufficient power to perform subgroup analysis on follicular, luteal or random start of ovarian stimulation. Our study showed that adding tamoxifen or letrozole to a standard ovarian stimulation protocol in women with breast cancer does not impact the effectiveness of fertility preservation and paves the way for high-quality long-term follow-up on breast cancer treatment outcomes and women's future pregnancy outcomes. Our study also highlights the need for high-quality studies for all women opting for fertility preservation, as alternative ovarian stimulation protocols have been introduced to clinical practice without proper evidence. The study was supported by a grant (2011.WO23.C129) of 'Stichting Pink Ribbon', a breast cancer fundraising charity organization in the Netherlands. M.G., C.B.L. and R.S. declared that the Center for Reproductive Medicine, Amsterdam UMC (location VUMC) has received unconditional research and educational grants from Guerbet, Merck and Ferring, not related to the presented work. C.B.L. declared a speakers fee for Inmed and Yingming. S.C.L. reports grants and non-financial support from Agendia, grants, non-financial support and other from AstraZeneca, grants from Eurocept-pharmaceuticals, grants and non-financial support from Genentech/Roche and Novartis, grants from Pfizer, grants and non-financial support from Tesaro and Immunomedics, other from Cergentis, IBM, Bayer, and Daiichi-Sankyo, outside the submitted work; In addition, S.C.L. has a patent UN23A01/P-EP pending that is unrelated to the present work. J.M.J.S. reported payments and travel grants from Merck and Ferring. C.C.M.B. reports her role as unpaid president of the National guideline committee on Fertility Preservation in women with cancer. K.F. received unrestricted grants from Merck Serono, Good Life and Ferring not related to present work. K.F. declared paid lectures for Ferring. D.S. declared former employment from Merck Sharp & Dohme (MSD). K.F. declared paid lectures for Ferring. D.S. reports grants from MSD, Gedeon Richter and Ferring paid to his institution; consulting fee payments from MSD and Merck Serono paid to his institution; speaker honoraria from MSD, Gedeon Richter, Ferring Pharmaceuticals and Merck Serono paid to his institution. D.S. has also received travel and meeting support from MSD, Gedeon Richter, Ferring Pharmaceuticals and Merck Serono. No payments are related to present work. NTR4108. 6 August 2013. 30 January 2014.

Prognostic and Predictive Value of CCND1/Cyclin D1 Amplification in Breast Cancer With a Focus on Postmenopausal Patients: A Systematic Review and Meta-Analysis.

BackgroundUp to 80% of breast cancers (BCa) are estrogen receptor positive and current treatments target the estrogen receptor (endocrine therapies) and/or CDK4/6 (CDK4/6 inhibitors). CCND1 encodes the protein cyclin D1, responsible for regulation of G1 to S phase transition in the cell cycle. CCND1 amplification is common in BCa and contributes to increased cyclin D1 expression. As there are signalling interactions between cyclin D1 and the estrogen receptor, understanding the impact of CCND1 amplification on estrogen receptor positive patients’ disease outcomes, is vital. This review aims to evaluate CCND1 amplification as a prognostic and predictive biomarker in BCa.Materials and MethodsPublications were retrieved from the databases: PubMed, MEDLINE, Embase and Cochrane library. Exclusion criteria were duplication, publication type, non-English language, in vitro and animal studies, not BCa, male BCa, premenopausal BCa, cohort size <35, CCND1 amplification not reported. Publications with cohort duplication, and inadequate recurrence free survival (RFS) and overall survival (OS) data, were also excluded. Included publications were assessed for Risk of Bias (RoB) using the Quality In Prognosis Studies tool. Statistical analyses (Inverse Variance and Mantel-Haenszel) were performed in Review Manager. The PROSPERO registration number is [CRD42020208179].Results CCND1 amplification was significantly associated with positive estrogen receptor status (OR:1.70, 95% CI:1.19-2.43, p = 0.004) and cyclin D1 overexpression (OR: 5.64, 95% CI: 2.32-13.74, p=0.0001). CCND1 amplification was significantly associated with shorter RFS (OR: 1.64, 95% CI: 1.13-2.38, p = 0.009), and OS (OR: 1.51, 95% CI: 1.19-1.92, p = 0.0008) after removal of studies with a high RoB. In endocrine therapy treated patients specifically, CCND1 amplification predicted shorter RFS (HR: 2.59, 95% CI: 1.96-3.41, p < 0.00001) and OS (HR: 1.59, 95% CI: 1.00-2.49, p = 0.05) also after removal of studies with a high RoB.ConclusionWhile a lack of standardised approach for the detection of CCND1 amplification is to be considered as a limitation, CCND1 amplification was found to be prognostic of shorter RFS and OS in BCa. CCND1 amplification is also predictive of reduced RFS and OS in endocrine therapy treated patients specifically. With standardised methods and cut offs for the detection of CCND1 amplification, CCND1 amplification would have potential as a predictive biomarker in breast cancer patients.Systematic Review Registration https://www.crd.york.ac.uk/prospero/, identifier CRD42020208179.

Prediction of Sentinel Lymph Node Biopsy Status in Breast Cancers with PET/CT Negative Axilla.

Background and Aim Prior knowledge of axillary node status can spare a lot of patients with early breast cancer morbidity due to an unnecessary axillary dissection. Our study compared various metabolic and pathological features that can predict the sentinel lymph node biopsy (SLNB) status in patients with positron emission tomography/computed tomography (PET/CT) negative axilla. Patients and Methods All consecutive patients with early breast cancers (< 5 cm) with PET/CT negative axilla who underwent breast surgery and SLNB from November 2016 to February 2020 were included. Various primary tumor (PT) pathological variables and metabolic variables on PET/CT such as maximum standardized uptake value (PT-SUV max ), metabolic tumor volume (PT-MTV), and total lesion glycolysis (PT-TLG) were compared using univariate and multivariate analyses for prediction of SLNB status. Results Overall 70 patients, all female, with mean age 55.6 years (range: 33–77) and mean tumor size 2.2 cm (range: 0.7–4.5), were included. SLNB was positive in 20% of patients ( n = 14) with nonsentinel nodes positive in 4% ( n = 3) patients. Comparing SLNB positive and negative groups, univariate analysis showed significant association of SLNB with low tumor grade, positive lymphovascular invasion (LVI), positive estrogen receptor (ER) status with lower mean K i -67 index (34.41 vs. 52.02%; p = 0.02), PT-SUV max (5.40 vs. 8.68; p = 0.036), PT-MTV (4.71 cc vs. 7.46 cc; p = 0.05), and PT-TLG (15.12 g/mL.cc vs. 37.10 g/mL.cc; p = 0.006). On multivariate analysis, only LVI status was a significant independent predictor of SLNB status (odds ratio = 6.23; 95% confidence interval: 1.15–33.6; p = 0.033). Conclusion SLNB is positive in approximately 20% of early breast cancers with PET/CT negative axilla and SLNB status appears to be independent of PT size. SLNB+ PTs were more likely to be LVI+ and ER + ve, with lower grade/K i -67/metabolic activity (SUV max /MTV/TLG) compared with SLNB–ve tumors. Logistic regression analysis revealed LVI status as the only significant independent predictor of sentinel lymph node status.

PD44-12 VAGINAL ESTROGEN THERAPY FOR GENITOURINARY SYNDROME OF MENOPAUSE (GSM) IN WOMEN WITH A PERSONAL HISTORY OF BREAST CANCER - A CLAIMS DATABASE ANALYSIS

You have accessJournal of UrologyCME1 May 2022PD44-12 VAGINAL ESTROGEN THERAPY FOR GENITOURINARY SYNDROME OF MENOPAUSE (GSM) IN WOMEN WITH A PERSONAL HISTORY OF BREAST CANCER - A CLAIMS DATABASE ANALYSIS Kathryn Dumas, Sajya Singh, Jaden R. Kohn, Taylor P. Kohn, and Marisa Clifton Kathryn DumasKathryn Dumas More articles by this author , Sajya SinghSajya Singh More articles by this author , Jaden R. KohnJaden R. Kohn More articles by this author , Taylor P. KohnTaylor P. Kohn More articles by this author , and Marisa CliftonMarisa Clifton More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002605.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Systemic therapies for breast cancer - selective estrogen receptor modulators (SERM), aromatase inhibitors (AI), and chemotherapies - can result in genitourinary syndrome of menopause (previously recognized as vulvovaginal atrophy) for up to 70% of postmenopausal breast cancer survivors. While systemic estrogen therapy is often avoided in these women, vaginal estrogen can be safely used to treat GSM symptoms. Our objective is to assess the use of vaginal estrogen for women with a diagnosis of GSM and a personal history of breast cancer using a large US claims database. METHODS: The TriNetX Diamond network database was queried: a US health research network of 190 million patients, encompassing healthcare encounters and prescriptions between 2009-2021. Females with a diagnosis of postmenopausal atrophic vaginitis or atrophy of the vulva (ICD-10 N95.2, N90.5) were included. Of these, women with breast cancer (C50 or Z86.000) were included if the diagnosis was at least 1 month prior to VVA diagnosis. Estrogen receptor status was collected when available (ICD-10 Z17.0, Z17.1). Prescriptions for treatment of GSM were included if prescribed the day of VVA diagnosis up to 1 year after index diagnosis. Incidence of vaginal estrogen use in patients with a history of breast cancer was determined for 2013-2015, 2016-2018, and 2019 to present. RESULTS: A total of 2,159,766 women with GSM were identified; of whom, 4.8% (n=104,327) had a personal history of breast cancer. Vaginal estrogen prescriptions were less frequent in women with history of breast cancer compared to women without (11% vs 22%, p<0.01, Table 1). Incidence rate of vaginal estrogen prescriptions for women with GSM and history of breast cancer remained stable around 10-11% from 2013 to present. 25,410 women with GSM and history of breast cancer had positive estrogen receptor status (ER+) and 4,893 had negative estrogen receptor status (ER-). There was no difference in vaginal estrogen prescribing between ER+ and ER- patients (7.4% vs 8.4%). CONCLUSIONS: While vaginal estrogen can be safely used in women with GSM and personal history of breast cancer, it is prescribed for few eligible patients. Barriers to use of vaginal estrogen in this population should be explored to optimize patient’s quality of life. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e712 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kathryn Dumas More articles by this author Sajya Singh More articles by this author Jaden R. Kohn More articles by this author Taylor P. Kohn More articles by this author Marisa Clifton More articles by this author Expand All Advertisement PDF DownloadLoading ...

Intraoperative radiation therapy for early stage breast cancer

Background and objectiveWe report our experiences with Intraoperative radiation therapy (IORT) among breast cancer (BC) patients in our region.MethodsAll patients who received radical IORT from April 2014 on to March 2020 were included in the study. Patient selection criteria included: Age equal or older than 45 years old; All cases of invasive carcinomas (in cases of lobular carcinomas only with MRI and confirmation); Patients who were 45–50 years old with a tumor size of 0–2 cm, 50–55 years old with a tumor size of < 2.5 cm, and those who were ≥ 55 years old with a tumor size of < 3 cm; Invasive tumors only with a negative margin; Negative nodal status (exception in patients with micrometastasis); A positive estrogen receptor status. Primary endpoints included death and recurrence which were assessed using the Kaplan–Meier method.ResultsOverall, 252 patients entered the study. Mean (SD) age of patients was 56.43 ± 7.79 years. In total, 32.9% of patients had a family history of BC. Mean (SD) tumor size was 1.56 ± 0.55 cm. Mean (IQR) follow-up of patients was 36.3 ± 18.7 months. Overall, 8 patients (3.1%) experienced recurrence in follow-up visits (disease-free-survival of 96.1%), among which four (1.5%) were local recurrence, two (0.8%) were regional recurrence and two patients (0.8%) had metastasis. Median (IQR) time to recurrence was 46 (22, 53.7) months among the eight patient who had recurrence. Overall, one patient died due to metastasis in our series. Eleven patients (4.3%) with DCIS in our study received IORT. All these patients had free margins in histopathology examination and none experienced recurrence.ConclusionInhere we reported our experience with the use of IORT in a region where facilities for IORT are limited using our modified criteria for patient selection.

Expression of Poly(Adenosine Diphosphate-Ribose) Polymerase Protein in Breast Cancer.

The use of poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors for breast cancer (BC) therapy is the subject of debate, and there is an urgent need to understand much the expression and prognostic role of the PARP1 protein. In this study, we have compared the expression of PARP between BC and benign breast disease (BBD) patients and also analyzed the association of PARP expression with clinicopathological parameters in BC. The study consists of 30 patients with newly diagnosed operable BC who were planned for surgery without neoadjuvant chemotherapy and 15 patients of BBD as a control between 2019 and 2021. Immunohistochemical analyses were performed prospectively on tissue samples. Anti-human PARP1 rabbit polyclonal antibody gives strong nuclear positivity. Internal control was the adipose tissue and the BBD acted as the external control. PARP1 expression was evaluated using the multiplicative quickscore method. The mean age for BC patients was 51.30 ± 10.694 years (range: 25-75 years) while BBD was below 30 years. Overexpression of PARP was present in 25 (83.3%) and weak expression in 5 (16.7%) of BC patients compared to BBD, only 2 (13.3%) patients demonstrated an overexpression of PARP, and 13 (86.6%) patients showed weak expression which showed significant association (P < 0.001). In BC, nuclear PARP (nPARP) overexpression was seen in 22 (73.3%) patients and weak expression of nPARP in 8 (26.7%), whereas 5 (16.7%) patients showed cytoplasmic overexpression. On comparing expression of PARP with clinicopathological parameters, PARP overexpression was significantly associated with older population (age >50 years) (P = 0.002), postmenopausal women (P = 0.029), higher TNM stage (Stage II and III) (P = 0.014), higher histological grade (grade 2) (P = 0.043), and presence of lymphovascular invasion (P = 0.015). Enhanced PARP1 expression is closely correlated with positive estrogen receptor status (P = 0.001) and PR status (P = 0.001). Overall PARP and nPARP overexpression was significantly associated with ER- (P = 0.006 and P = 0.008) and PR-positive (P = 0.006 and P = 0.008) patients. The PARP and nPARP overexpression was significantly associated with nontriple-negative BC patients (P = 0.001 and P = 0.001). We have not come across any study in the literature to compare PARP expression in BC and BBD patients. On the basis of our observations, we concluded that PARP overexpression is a poor prognostic marker in BC.

Gastrin-Releasing Peptide Receptor Antagonist [68Ga]RM2 PET/CT for Staging of Pre-Treated, Metastasized Breast Cancer.

Simple Summary[68Ga]RM2 positron emission tomography (PET)/computed tomography (CT) has shown to be a promising imaging method for primary breast cancer (BC) with positive estrogen receptor (ER) status, but it has not been tested for visualization of metastasized recurrent or progressive BC. The aim of this pilot study was to assess tumor visualization using [68Ga]RM2 PET/CT in patients with pre-treated ER-positive BC and suspected metastases. Eight female patients with initial ER-positive, pre-treated BC were included in this retrospective study. Strong RM2 binding was found in all metastatic lesions of six patients, whereas two patients were rated RM2-negative. Our data suggest that RM2 binding is maintained in the majority of patients with advanced disease stage of pre-treated ER-positive BC. Thus, [68Ga]RM2 PET/CT could support treatment decision in these patients, radiotherapy planning in oligometastatic patients or selection of patients for RM2 radioligand therapy.Background: Positron emission tomography (PET)/computed tomography (CT) using the gastrin-releasing peptide receptor antagonist [68Ga]RM2 has shown to be a promising imaging method for primary breast cancer (BC) with positive estrogen receptor (ER) status. This study assessed tumor visualization by [68Ga]RM2 PET/CT in patients with pre-treated ER-positive BC and suspected metastases. Methods: This retrospective pilot study included eight female patients with initial ER-positive, pre-treated BC who underwent [68Ga]RM2 PET/CT. Most of these patients (seven out of eight; 88%) were still being treated with or had received endocrine therapy. [68Ga]RM2 PET/CTs were visually analyzed by two nuclear medicine specialists in consensus. Tumor manifestations were rated qualitatively (i.e., RM2-positive or RM2-negative) and quantitatively using the maximum standardized uptake value (SUVmax). SUVmax values were compared between the two subgroups (RM2-positive vs. RM2-negative). Results: Strong RM2 binding was found in all metastatic lesions of six patients (75%), whereas tracer uptake in all metastases of two patients (25%) was rated negative. Mean SUVmax of RM2-positive metastases with the highest SUVmax per patient (in lymph node and bone metastases; 15.8 ± 15.1 range: 3.7–47.8) was higher than mean SUVmax of the RM2-negative metastases with the highest SUVmax per patient (in bone metastases; 1.6 ± 0.1, range 1.5–1.7). Conclusions: Our data suggest that RM2 binding is maintained in the majority of patients with advanced disease stage of pre-treated ER-positive BC. Thus, [68Ga]RM2 PET/CT could support treatment decision in these patients, radiotherapy planning in oligometastatic patients or selection of patients for RM2 radioligand therapy. Further studies with larger patient cohorts are warranted to confirm these findings.

Impact of BRCA mutations and hormone receptor status on reproductive potential in breast cancer patients undergoing fertility preservation

Objective To identify whether the BRCA mutations and hormone receptor status affect the ovarian reserve and ovarian stimulation outcomes in breast cancer patients undergoing fertility preservation. Methods A total of 117 women diagnosed with breast cancer who were referred to the fertility preservation clinics at Seoul National University Bundang Hospital and Seoul National University Hospital between September 2012 and July 2019 undergone ovarian stimulation for oocyte retrieval. Basal characteristics including age, BMI, basal AMH, basal FSH, and fertility preservation outcomes such as the number of retrieved oocytes and mature oocytes were compared retrospectively. Results BRCA1 mutation was noted in 25 women, and BRCA2 mutation was observed in 35 women. Positive estrogen receptor status was noted in 87 women, and positive progesterone receptor status was noted in 69 women. HER2 was positive in 55 women, and 19 women were diagnosed with triple-negative breast cancers. The number of total oocytes retrieved was lower in patients with BRCA mutation (8.3 ± 5.4 vs. 15.3 ± 8.7, p = .002). The number of mature oocytes retrieved was also lower in BRCA carriers (4.7 ± 4.2 vs. 8.7 ± 7.9, p = .025). Triple-negative breast cancer (TNBC) patients were younger than non-TNBC patients (30.3 ± 4.8 vs. 33.9 ± 5.0, p = .007). The rate of mature oocyte rate was higher in TNBC patients (68.6%±20.6 vs. 52.5%±29.7, p = .037). Conclusions Our study demonstrated that BRCA carriers with breast cancer had comparable ovarian reserve to non-carriers but the response to ovarian stimulation was lower. We also observed that oocyte maturity was higher in TNBC patients, however age might be a confounding factor of this result.

Dosimetry and outcomes in patients receiving radiotherapy for synchronous bilateral breast cancers

BackgroundSynchronous bilateral breast cancer (SBBC) is rare and there is little evidence describing organs at risk (OAR) and limits to the heart and lungs caused by radiotherapy (RT). Quantifying mean heart dose (MHD) and mean lung dose (MLD) from RT in this patient cohort may lead to better understanding of doses to OAR and resultant effects on clinical outcomes. The primary objective was to assess median MHD and MLD in SBBC, while secondary aims included analyses of 1) factors associated with MHD and MLD, 2) V5 and V20 values and 3) factors associated with clinical outcomes. MethodsPatients planned for adjuvant bilateral whole breast/chest wall (WB) RT from a single institution treated in 2011-2018 were included. Median MHD and MLD (Gy) were stratified by hypofractionated (42.56 Gy/16 fractions, HFRT) and conventional fractionation (50 Gy/ 25 fractions, CFRT) and summarized separately based on the following treatments: 1) locoregional RT, WB tangential RT either 2) no boost 3) sequential boost or 4) simultaneous integrated boost. MHD, MLD, lung V5 and V20 values, and demographics were collected. Linear regression analyses identified factors associated with MHD and MLD and factors associated with clinical outcomes. ResultsA total of 88 patients were included. The median MHD for HFRT and CFRT was 1.99 Gy and 2.94 Gy, respectively. The median MLD for HFRT and CFRT was 6.00 Gy and 10.08 Gy, respectively. MHD and MLD were significantly associated with the occurrence of a cardiac or pulmonary event post-radiation. Patients who had a mastectomy or tumoral muscle involvement were more likely to develop a local recurrence, metastasis or new primary while patients who had a lumpectomy or tumor with a positive estrogen receptor status were less likely to experience these events. ConclusionsFurther investigation should be conducted to identify SBBC RT techniques that mitigate dose to OARs to improve clinical outcomes in bilateral breast patients.