Progesterone Receptor Positivity Research Articles

CORRELATION OF RECEPTOR STATUS WITH AXILLARY NODAL METASTASIS AND OTHER PROGNOSTIC FACTORS IN CARCINOMA BREAST : INDIAN PERSPECTIVE

Background- nd Breast cancer is the 2 most common cancer globally and it ranks rst in India. The predictive value of various components like hormone receptor status, tumor size, grade to axillary lymph nodal metastasis has been studied previously. Our aim is to study the correlation of receptor status and axillary lymph nodal metastasis in breast cancer patients. Methods- This is a retrospective study carried out in single surgical unit. 104 biopsy proven unilateral breast cancer patients who underwent modied radical mastectomy has been reviewed. The clinicopathological data has been collected from hospital records. Results- The mean age of presentation is 42.2years. Most common age group is 30-49years with clinical stage III(65.38%) with inltrating ductal carcinoma(99.03%). Although axillary lymph node was palpable in 75%, nodal metastasis is present in 63.46% of patients. Positive estrogen receptor, progesterone receptor and Her2 receptors are seen in 45.19%, 34.6% and 59.61% patients respectively. TNBC patients has least while triple positive has maximum nodal metastasis in our study group. Perineural invasion and extra capsular extension is seen in 15.38% each and lymphovascular invasion is seen in 38.4% patient. Although LVI, PNI and ECE is predominant in Her2-enriched subtypes, most patients belonging to HR+/Her2+ subtypes has LVI, PNI and ECE. TNBC and HR+/Her2- subtypes has least LVI, PNI and ECE. Conclusion- Receptor status has signicant role in predicting nodal metastasis. TNBC, although considered most aggressive, has least axillary nodal metastasis suggesting less lymphatic involvement and less LVI, PNI and ECE. Also Her2 over-expression seems to be related to nodal metastasis, LVI, PNI and ECE, suggesting there may be some pathway which is still unrevealed. Thus Her2 receptor positivity can be considered as an independent poor prognostic factor.

Palbociclib and letrozole in hormone-receptor positive advanced breast cancer: Predictive response and prognostic factors

CDK 4/6 inhibitors have been yielding propitious results when with hormone therapy in the management of Her2-negative and hormone-receptor (HR)-positive metastatic breast cancer, palbociclib being one of the first molecules investigated in this setting. However, the response to CDK4/6 inhibitors is variable. To identify predictive and prognostic factors of response to this therapeutic regimen. Eligible patients were females with HR+ and Her2- advanced breast cancer, receiving Palbociclib in combination with Letrozole. PFS was the primary endpoint in the evaluation of response to treatment. This survival was then further segregated according to various characteristics: histological (type, grade, hormone receptors), metastatic site, line of treatment, response type at initial assessment, and best response achieved. The data was then processed by two statistical analysis models: Kaplan-Meier and univariate preceding multivariate Cox proportional risks. Sixty patients were included and followed for a median follow-up duration of 15.98 months. PFS recorded a median of 19.07 months (95% CI=15.43-22.71). PFS had a median of 12.99 months in the absence of progesterone receptors (vs 20.05 months in the case of positive estrogen and progesterone receptors; P = 0.046), a median of 13.02 months in the presence of liver metastases (vs 22.98 months in the absence of liver metastases; P = 0.007), and 15.94 months in the case of second-line and beyond (vs 22.98 months in the case of first-line; P = 0.033). Regarding the Hazard Ratio of progression, we note age (HR 0.941; P = 0.019), liver metastases (HR 2.751; P = 0.051), response at initial evaluation (HR<1; P < 0.001) and best response (HR<1; P = 0.003). PFS reached similar figures to those of international studies. The absence of progesterone receptors, presence of liver metastases, and use as second-line or beyond are associated with a reduced median PFS. One year age increase (protective factor), liver metastases (risk factor), response at initial evaluation, and best response achieved are identified as the most predictive factors of the response to this treatment regimen and of the progression risk.

Relation of Receptor Status and Tumor Grade with Menopausal Status in Patients of Carcinoma Breast

Background: Carcinoma of the breast is the most common female cancer and its incidence is rapidly increasing over the last few decades. In Bangladesh, breast cancer is an issue of gaining concern. Receptor status and histological grade are two important prognostic factors of carcinoma breast. Aim of the study: To assess the relation and distribution of receptor status and tumor grade among pre and postmenopausal patients of carcinoma breast. Methods: This cross-sectional observational study was carried out in the Department of General Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU) Dhaka over a period of one year, a total of 59 admitted female patients with histologically proven carcinoma of the breast were divided into two groups included in this study. The premenopausal age group was considered as a group I (n=31) and the postmenopausal age group was considered as group II (n=28). Data regarding the tumor histopathological type, grading, and receptor status along with other variables were included in a pre-designed data collection sheet. After compiling data, Statistical analyses of the data were done with Statistical Packages for Social Sciences (SPSS- 22). Results: Sociodemographic variables and personal histories leading to a risk of breast cancer have no significant difference between pre and postmenopausal groups. Invasive ductal carcinoma (grade-II) was predominant in both groups. Estrogen and progesterone receptor-negative tumors were more frequent in premenopausal patients and estrogen and progesterone receptor-positive tumors were more frequent in a postmenopausal patient, but no statistically significant difference between the two groups. More than eighty percent of tumors were human epidermal growth factor-2 negative in both groups. The frequency of estrogen and progesterone receptor positivity gradually reduce from grade I to III in both groups and the frequency of estrogen and progesterone receptor negativity gradually increase from grade

Progesterone Receptor Status of Epithelial Cells as a Predictive Marker for Postoperative Recurrence of Endometriosis.

Progesterone resistance including progesterone receptor (PR) deficiency contributes to the pathophysiology of endometriosis; however, whether the PR expression levels in ovarian endometrioma (OE) correlate with the postoperative recurrence of endometriosis remains unclear. This study aimed to investigate the association between PR expression levels in OE and the recurrence of endometriosis. OE specimens were obtained from 132 patients who underwent conservative surgery for endometriosis. The PR expression levels were evaluated using the H score after immunohistochemical staining. Of the 132 patients, 36 (27.3%) experienced recurrence and 96 (72.7%) did not. No differences were observed in the patient characteristics between the recurrence and nonrecurrence groups except for follow-up period. PR immunoreactivity in the epithelial cells (ECs) was statistically significantly lower in the recurrent group than in the nonrecurrent group (P < .01); however, this change was not observed in the stromal cells. Moreover, multivariable logistic regression analysis revealed that the H score of PR in ECs was an independent factor and was statistically significantly associated with the recurrence of endometriosis (P = .01). Furthermore, we divided the patients into PR-negative or PR-positive groups. The cumulative recurrence rate in the negative PR group was statistically significantly higher than that in the positive PR group (P = .046). Low PR expression levels in OE-ECs may predict the recurrence of endometriosis. The PR status in OE-ECs is associated with the pathophysiology of the recurrence of endometriosis, and optimized postoperative management for endometriosis may be provided by referring to the PR status.

Treatment results and patient characeristics for breast cancer patients older than 70 Years

Objective: The incidence of breast cancer (BC) subtypes varies according to age, and its treatment is more strenuous and requires much more attention in advanced ages. The aim of this study is to investigate patient characteristics and treatment results respectively for patients older than 70 years. Materials and Methods: In this study, we examined 188 elderly BC patients treated in our hospital, at March 2008 - November 2019. Patient characteristics and demographics were investigated from patients’ files retrospectively. Results: Mean age of the patients was 74.3 ± 4 years (All female). The presence of comorbid diseases was 76.1%. Major histology was invasive ductal carcinoma in 72.9% and mostly grade 2 differentiated, and the majority of patients were T2 size (58.5%). Oestrogen receptor (OR) positivity was seen in 83%, Progesterone receptor (PR) positivity in 72.3% of patients and cerb2 positivity in 16.5%. Luminal B (47.9%) was the most common in molecular subgroup analysis. Patients with lymph node involvement (N1 33%; N2, 19.1%; N3, 6.9%) were higher than those without involvement (34%). Surgery type was modified radical mastectomy (MRM) for 51.6%, breast conserving surgery (BCS) for 39.4 % and lumpectomy for 7.4%. In a median follow-up time was 53.9 (9-101) months, local recurrence was seen in 5 (2.7%) patients and distant metastasis was developed in 16 (8.5%) patients. The median overall survival was worse in those with MRM than those with BSC (p=0.006). In multivariate logistic regression analysis, only found that lymph node positivity was an independent risk factor for metastasis (HR; 4.15, 95% CI:1.019-16.933, P=0.047). Conclusion: While it was observed that the most important risk factor for metastasis risk in elderly patients was lymph node positivity; The hormonal status and her2 conditions were not affected in terms of metastasis. It was thought that tumor clinical course and relapse may differ in the elderly population compared to general BC patients.

Evaluation of Breast Cancer Size Measurement by Computer-Aided Diagnosis (CAD) and a Radiologist on Breast MRI.

Purpose: This study aimed to evaluate cancer size measurement by computer-aided diagnosis (CAD) and radiologist on breast magnetic resonance imaging (MRI) relative to histopathology and to determine clinicopathologic and MRI factors that may affect measurements. Methods: Preoperative MRI of 208 breast cancers taken between January 2017 and March 2021 were included. We evaluated correlation between CAD-generated size and pathologic size as well as that between radiologist-measured size and pathologic size. We classified size discrepancies into accurate and inaccurate groups. For both CAD and radiologist, clinicopathologic and imaging factors were compared between accurate and inaccurate groups. Results: The mean sizes as predicted by CAD, radiologist and pathology were 2.66 ± 1.68 cm, 2.54 ± 1.68 cm, and 2.30 ± 1.61 cm, with significant difference (p < 0.001). Correlation coefficients of cancer size measurement by radiologist and CAD in reference to pathology were 0.898 and 0.823. Radiologist’s measurement was more accurate than CAD, with statistical significance (p < 0.001). CAD-generated measurement was significantly more inaccurate for cancers of larger pathologic size (>2 cm), in the presence of an extensive intraductal component (EIC), with positive progesterone receptor (PR), and of non-mass enhancement (p = 0.045, 0.045, 0.03 and 0.002). Radiologist-measured size was significantly more inaccurate for cancers in presence of an in situ component, EIC, positive human epidermal growth factor receptor 2 (HER2), and non-mass enhancement (p = 0.017, 0.008, 0.003 and <0.001). Conclusion: Breast cancer size measurement showed a very strong correlation between CAD and pathology and radiologist and pathology. Radiologist-measured size was significantly more accurate than CAD size. Cancer size measurement by CAD and radiologist can both be inaccurate for cancers with EIC or non-mass enhancement.

Abstract P1-19-03: Phase II trial of durvalumab and tremelimumab in the hormone receptor-positive metastatic breast cancer with high tumor mutational burden selected by whole exome sequencing: Korean cancer study group trial (KCSG BR17-04)

Abstract Background: Hormone-receptor (HR) positive breast cancer is the main subtype of breast cancer. Although overall survival of HR-positive metastatic breast cancer (MBC) patients has improved by various therapies including endocrine therapies, CDK4/6 inhibitors, and cytotoxic chemotherapy, it is still considered incurable. Immune checkpoint inhibitors have rarely been clinically tested in HR-positive breast cancer, despite proving anti-cancer activity in early and metastatic triple-negative breast cancer in various trials. We evaluated efficacy and safety of combined durvalumab and tremelimumab in the HR-positive MBC, which was enriched with high tumor mutational burden (TMB). Methods: HR-positive MBC patients who received prior 1 or more lines of therapy in metastatic setting were prescreened with whole exome sequencing (WES) using metastatic or recurred tumor biopsies. Criterion of high TMB was defined as upper 30%. In the beginning, the criterion of high TMB was 2.1 mutations per Mb, based on the retrospective WES database in Yonsei Cancer Center and this criterion was recalculated every 30 cases. Patients who met upper 30% of TMB were treated with combined durvalumab (1500mg every 4 weeks upto 13 doses) and tremelimumab (75mg every 4 weeks upto 4 doses). Response was evaluated every 2 cycles using RECIST 1.1 and toxicity was evaluated using NCI-CTCAE 4.03. Tumor-infiltrating lymphocyte (TIL) and PD-L1 expression were also analyzed to investigate a correlation with TMB. Results: Biopsies of recurrent or metastatic tumors were taken from a total of 119 patients for WES assay. A median turn-around-time of TMB data was 30.0 days (range, 16~67). Of these 119 patients, a median number of nonsynonymous mutations was 2.0 per Mb (range, 0~21.7) with upper 30% criterion of 3.1. High TMB showed a trend toward old age (P=0.074) and single positivity of estrogen receptor (ER) or progesterone receptor (PR) compared to positivity of both ER and PR (P=0.055). TMB was positively correlated with TILs (r=0.289, P=0.005). Thirty patients with high TMB received study treatment with a median 2 cycles (range, 1~13). A median prior lines of therapies in metastatic setting was 4 (range, 1~9). The objective response and clinical benefit rates were 6.3% (2 PRs of 30) and 20% (2 PRs plus 4 SDs of 30). There was one treatment-related mortality due to pneumonitis. Immune-related adverse events included endocrinopathy (n=3; hypothyroidism in 2, hyperthyroidism in 1), enteritis (n=2), skin rash (n=2), pneumonitis (n=1), and so on. Biomarker analyses are underway. Conclusions: WES-based TMB using metastatic tumor biopsy was a feasible platform to prescreen HR-positive MBC patients. Combined durvalumab and tremelimumab showed a modest activity and good tolerability in heavily treated, HR-positive MBC with high TMB. Citation Format: Yong Wha Moon, Eunyoung Kim, Min Hwan Kim, Gun Min Kim, Seul-Gi Kim, YeeSoo Chae, Jieun Lee, Jae Ho Jeong, Kyung-Hun Lee, Han Jo Kim, Joo Young Jung, Su-Jin Koh, Kyoung Eun Lee, Hee-Jun Kim, Kyong Hwa Park, Seungtaek Lim, Yeon Hee Park, Tae Hoen Kim, Sewha Kim, Yohan Yang, Sangwoo Kim, Joohyuk Sohn. Phase II trial of durvalumab and tremelimumab in the hormone receptor-positive metastatic breast cancer with high tumor mutational burden selected by whole exome sequencing: Korean cancer study group trial (KCSG BR17-04) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-19-03.

Abstract P3-19-12: Impact of endocrine therapy (ET) noncompliance following intra-operative radiation therapy (IORT) in treatment of early-stage breast cancer patients (pts) enrolled in the ExBRT trial

Abstract Purpose: To investigate the association between ET noncompliance and ipsilateral breast tumor recurrence (IBTR) in the ExBRT trial (“A Safety and Efficacy Study of Intra-Operative Radiation Therapy [IORT] Using the Xoft® Axxent® Electronic Brachytherapy [eBx®] System at the Time of Breast Conservation Surgery for Early-Stage Breast Cancer”). Methods: The IRB-approved single arm prospective nonrandomized multi-institutional ExBRT trial was designed to determine the efficacy and outcome of a single 20 Gy fraction of IORT delivered at the time of lumpectomy for early-stage breast cancer. The trial included women age ≥ 40 years with invasive ductal carcinoma (IDC) or ductal carcinoma in situ (DCIS) of all molecular subtypes documented by pre-operative biopsy which were ≤ 30 mm by clinical and radiographic evaluation. Tumors with pre-operative lymphovascular invasion and intra-operative positive lymph nodes and/or margins were excluded. ET was defined as treatment with tamoxifen, anastrozole, letrozole, and/or exemestane. Pts were classified as “Compliant with ET” if they completed a 60-month ET course or were compliant with ongoing ET. Pts were defined as “Discontinued ET” if they stopped ET prior to completing a 60-month ET course. Pts were classified as “Declined ET” if they did not initiate recommended ET. Data, collected at enrollment and at 1, 6, 12, 18 and 24 months, then yearly, included demographics, histopathology, estrogen receptor positivity (ER+), progesterone receptor positivity (PR+), adjuvant therapy, IBTR, and survival. The primary endpoint was IBTR. Preliminary results evaluating the impact of ET noncompliance on pts who successfully completed treatment with a single 20 Gy fraction of IORT per protocol are presented. Results: Between May 2012 - July 2018, 1105 pts (mean age 64 years) with pre-operative biopsy-proven IDC or DCIS successfully completed a single fraction of IORT treatment per protocol. Mean follow-up was 4.0 years (range 2-8 years). One-hundred fifteen (10%) pts, who were either ER negative or had an unknown ER status, are not included in this analysis. Pt cohorts and tumor characteristics are presented in Table 1. There were 39 (3.93%) IBTR in the ER+ subset at mean follow-up of 4 years. IBTR in the “Compliant with ET” group was 2.53%. Although the percentages were greater in the “Discontinued ET” (5.68%) and “Declined ET” (7.10%) cohorts, this did not reach statistical significance (Chi square test, p-value = 0.147). Conclusion: IORT allows pts to conveniently receive both their surgery and electronic brachytherapy radiation treatment in one setting. Early-stage ER+ breast cancer pts compliant with a subsequent course of ET in this study experienced a lower IBTR rate, improving the collective outcome of their multidisciplinary treatment. These preliminary ExBRT trial results demonstrate that IBTR rates are improved with ET compliance. Although this has not reached statistical significance in this trial, it may partially explain the slight differences in IBTR rates noted in comparison with similar electronic brachytherapy early-stage breast cancer studies. Table 1.IORT pt cohorts and tumor characteristicsCompliant with ETDiscontinued ETDeclined ETNNNER +631176183PR +597170162Mean age (years)65.766.366.7Postmenopausal580162161Mean tumor size (mm)11.110.712.7Tumor HistologyIDC524136120grade I2116055grade II2535955grade III54159Unknown grade621DCIS933756Low grade2099Intermediate grade421925High grade30922Unknown grade100Infiltrating lobular ca505Other932Chemotherapy given4286Ethnicity/RaceCaucasian498143151African American351013Hispanic46188Asian/Pacific Islander2812Native American211Other2238Recurrences16 (2.53%)10 (5.68%)13 (7.10%) Citation Format: Barbara Schwartzberg, AMNisar Syed, Robert Cohen, William Dooley, Maen Farha, Veronica Jones, Wesley Hodge. Impact of endocrine therapy (ET) noncompliance following intra-operative radiation therapy (IORT) in treatment of early-stage breast cancer patients (pts) enrolled in the ExBRT trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-12.

Abstract P3-14-16: Prevalence of low estrogen receptor and low progesterone receptor positivity at an urban safety net hospital

Abstract Background: The American Society of Clinical Oncologists/College of American Pathologists guidelines were updated in January 2020 to account for a range of positivity in Estrogen Receptor expression (ER), with samples with 1-10% immunoreactive tumor cell nuclei being reported as ER low positive (low+). There is limited data on endocrine responsiveness of this group and ER low+ cancers tend to profile and behave more like typical triple negative breast cancers (TNBC). The significance of isolated Progesterone Receptor (PR) expression is still unclear even though it is reported between 1-100%. This project investigated the number of ER low+ breast cancer patients at John Peter Smith Hospital (JPS). JPS has a higher proportion of Black breast cancer patients than SEER. As Black patients are more likely to have TNBC than non-Hispanic white patients (NHW), JPS also has a higher proportion of TNBC. With ER low+ cancers behaving more like TNBC, this research was conducted to see if there were also more ER low+ patients at JPS. Methods: A retrospective study was conducted using data from the institutional registry of the JPS Oncology and Infusion Center in Fort Worth, TX. Eligible patients were diagnosed with invasive breast cancer in 2020. Data from the JPS Department of Pathology and analyzed for ER and PR expression percentage, Her2 status, race, and ethnicity. HR+ was defined as either ER or PR being 10-100%. JPS data was compared to SEER data from 2014-2018. Results: JPS had 119 eligible patients for this study; 36 NHW, 31 Black, and 47 Hispanic. Of these, 6 were ER low+ and 4 of those were Her2-. 2 of the ER low+ patients were Black and 4 Hispanic. There were 96 Her2- patients, with 26 ER-, 4 ER low+, and 66 ER+. Of the overall 35 ER- patients, 34 were also PR- and 1 was PR low+. 4 of the 6 ER low+ were PR- and 2 PR low+. Conclusion: JPS has a higher percentage of ER low+ cases than previous studies conducted, with 2.6% and 1% found in literature review and 5% (95% CI: 1%, 9%) at JPS, but there is no national data to compare to yet. All the ER low+ patients at JPS were Black or Hispanic. This is limited by the number of ER low+ patients. Blacks and especially Hispanics were more likely to be ER- or ER low+ than NHW. They were also more likely to be PR-, with Black patients most likely to be PR low+. Black patients were most likely to be Her2-. For patients that were ER-, there was a strong concordance with PR status, with 1 case where PR was in a higher category and 86% of cases having ER and PR in agreement. Black and Hispanic patients account for 80% of TNBC at JPS. JPS has a significantly higher proportion of TNBC cases compared to SEER, with 21% (95% CI: 14%; 28%) of cases being TNBC and an additional 3.4% that are ER low+ and Her2-, therefore possibly behaving like TNBC. It is necessary to further investigate the significance of ER low+ and PR low+ expression, and for more research to be done on breast cancer in minority patients who are underrepresented in clinical trials but are more likely to have TNBC, which is aggressive and has poor survival rates. Percentage of Each Status by RaceER-ER low+ER+PR-PR low+PR+Her2-Her2+TNBCNon-Hispanic White22.2%(8)0%(0)77.8%(28)30.6%(11)5.6%(2)63.9%(23)77.8%(28)22.2%(8)20%(5)Black29%(9)6.5%(2)64.5%(20)41.9%(13)16.1%(5)41.9%(13)87.1%(27)9.7%(3)24%(6)Hispanic31.9%(15)8.5%(4)59.6%(28)51.1%(24)6.4%(3)42.6%(20)80.9%(38)19.1%(9)48%(12)Other50%(3)0%(0)33.3%(2)66.7% (4)0%(0)16.7%(1)66.7%(4)16.7% (1)8%(2)Overall29.4%(35)5%(6)64.7%(77)42.9%(51)8.4%(10)47.9 %(57)80.7%(96)17.6%(21)(25)*One patient was Black Hispanic and was included in both rows as ER+ PR- Her2- Comparison of Subtypes between JPS and SEERHR+ Her2-ER low+ PR- Her2-ER-PR low+ Her2 -HR-Her2- (TNBC)HR+ Her2+ER low+ PR- Her2+HR- Her2+UnknownJPS Cases by Subtype 202055.5% (66)3.4%(4)0.8%(1)21%(25)9.2%(11)1.7%(2)6.7%(8)1.7%(2)SEER Cases by Subtype 2014-201868%(included in HR+ Her2-)(included in HR+ Her2-)10%10%(included in HR+ Her2+)4%7% Citation Format: Callie Angell, Jolonda Bullock, Anna Diaz, Riyaz Basha, Kalyani Narra. Prevalence of low estrogen receptor and low progesterone receptor positivity at an urban safety net hospital [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-14-16.

Risk Association of TOX3 and MMP7 Gene Polymorphisms with Sporadic Breast Cancer in Mexican Women.

Breast cancer (BC) has one of the highest incidences and mortality worldwide. Single nucleotide polymorphisms (SNPs) in TOX3 rs3803662 and MMP7 rs1943779 have been associated with susceptibility to BC. In this case-control study, we evaluated the association of rs3803662 (TOX3)/rs1943779 (MMP7) SNPs with clinical features, immunohistochemical reactivity, and risk association with BC in women from northeastern Mexico. We compared 212 BC cases and 212 controls. DNA was isolated from peripheral blood to perform the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. We calculated genotype frequencies, odds ratios, and 95% confidence intervals. We found that CT (Cytocine–Thymine) and TT (Thymine –Thymine) genotypes, and T alleles of TOX3 rs3803662, were associated with BC risk (p = 0.034, p = 0.011, respectively). SNP TOX3 rs3803662 was associated with positive progesterone receptors (PR) and triple-negative BC (TNBC) but not with estrogen receptor (ER) or HER2 reactivity. CT and TT genotypes (p = 0.006) and T alleles (p = 0.002) of SNP MMP7 rs1943779 were associated with risk of BC. We found that T alleles of TOX3 rs3803662 and MMP7 rs1943779 SNPs are associated with BC risk. These findings contribute to personalized medicine in Mexican women.

Puberty and sex in pediatric thyroid cancer: could expression of estrogen and progesterone receptors affect prognosis?

ObjectiveA sharp increase in pediatric thyroid cancer incidence is observed during adolescence, driven mainly by girls. Differences in disease presentation across sexual maturity stages raise the question of whether sex steroids have a role in the heterogeneity. The aims of this study were to analyze the influence of puberty and sex on clinical presentation and prognosis and to evaluate the correlation between the expression of sex hormone receptors.Design and methodsClinical records and immunohistochemical of specimens from 79 patients were analyzed. Puberty was analyzed by two criteria: end of puberty and beginning, in which the age of 10 was the cutoff.ResultsPostpubertal were more frequently classified as having low-risk disease and a lower frequency of persistent disease, especially when the completion of puberty was used as the criteria. Male sex was associated with a higher risk of persistent disease at the end of the observation period. Estrogen receptor α positivity was low in the entire sample, while progesterone receptor positivity was positive in 30% of the cases. Female hormone receptor expression was not associated with sex, American Thyroid Association risk score, persistent structural disease, or pubertal status.ConclusionOur study showed that the completion of puberty correlated best with the clinical behaviour of pediatric thyroid cancer. It was also shown that postpubertal patients have a less aggressive initial presentation and better outcomes. However, this observation could not be explained by the expression of estrogen and progesterone receptors in the primary tumors.

Correlation Between Age and Hormone Receptor Status in Women With Breast Cancer.

IntroductionBreast cancer is a leading cause of death among women. This study aimed to evaluate the association between age and hormonal receptor status (HRS) in women with breast cancer presented at a public hospital in Karachi, Pakistan.MethodsA cross-sectional study was conducted at the Department of Medical Oncology, Jinnah Postgraduate Medical Center (JPMC), Karachi, Pakistan, from January 2021 to August 2021. All women of age more than 18 years with a confirmed diagnosis of breast cancer were included in the study using non-random consecutive sampling techniques. Women who underwent artificial menopause or hysterectomy, women who had chemotherapy-induced menopause, and pregnant women were excluded from the study. Data were collected from all patients regarding socio-demographics and tumor characteristics. Immunohistochemistry (IHC) was performed to evaluate the status of hormonal receptors.ResultsThe mean age at the time of presentation of females with breast cancer was 46.57±11.45 years. Among 317 females, 180 females had positive estrogen receptor (ER) expression (56.8%), 173 had positive progesterone receptor (PR) expression (54.6%), and 121 had positive human epidermal growth factor receptor 2 (HER2/neu) expression (38.2%). The highest proportions of positive ER (36.7%), PR (38.2%), and HER/2 neu (37.2%) expression were observed in the age group 41-50 years, respectively. There was a statistically significant association between age and ER expression (p=0.017) and age and PR expression (p=0.003) while no association was found between age and HER/2 neu expression (p=0.335). ConclusionThe present study indicated that the majority of the patients were diagnosed with breast cancer in their 40s. Most of the women in the younger age groups were estrogen receptor (ER), progesterone receptor (PR), and HER2/neu negative while the older aged women were more frequently ER, PR, and HER2/neu positive albeit, the association between age or HER2/neu was not significant. In short, we can expect that the older aged patients may have better survival rates and patient prognosis. However, this is just a conjecture and further large-scale, multicenter, and long-term studies are required to understand the true relationship between age and patient survival rates. We hope that the current study will serve as a catalyst for future breast-cancer related studies.

Breast cancer recurrence: factors impacting occurrence and survival

BackgroundBreast cancer mortality has decreased due to improved screening and treatment options. Nevertheless, 25–30% of patients develop disease recurrence and die from the disease dissemination. Patients who develop metastatic disease represent a heterogeneous group and management plans are dependent on molecular subtype, disease burden and metastatic site.AimTo determine predictive clinicopathological factors of disease recurrence and their impact on survival in the molecular era.MethodsConsecutive patients who breast cancer developed recurrence at our tertiary referral centre between 2000 and 2015 were included. Clinicopathological and treatment data were assessed using descriptive statistics. Oncological outcome was assessed using Cox regression and Kaplan Meier analyses.ResultsTwo hundred sixty-five consecutive patients who developed breast cancer recurrence were included; median age at metastasis was 59.3 years (range 27–87 years), and median time to recurrence (TTR) was 47.7 ± 38.5 months (range 3.0–194.3 months). Survival was 24.2% (64/265) 53.2% were luminal A (LABC) (141/265), 18.5% were luminal B (LBBC) (49/265), 18.5% were triple negative (TNBC) (49/265), and 9.8% were human epidermal growth factor receptor-2 overexpressing (HER2 +) (26/265). TTR for patients with LABC was 56.0 ± 41.3 months, LBBC was 48.4 ± 41.1 months, TNBC was 26.9 ± 28.5 months and HER2 + was 34.3 ± 21.8 months. Increased grade (P < 0.001), Nottingham Prognostic Indices (P < 0.001), TNBC (P < 0.001), HER2 + subtype (P < 0.001) and receiving targeted therapy (P = 0.006) predicted shorted TTR. Estrogen receptor positivity (P < 0.001), progesterone receptor positivity (P = 0.010), invasive lobular carcinoma (P = 0.009) and receiving endocrine therapy (P = 0.001) predicted longer TTR.ConclusionReadily available clinicopathological factors predict risk of metastatic dissemination. Developing a tailored program to identify patients at risk of recurrence is crucial in controlling metastatic dissemination of breast cancer.

Mastectomy or Margin Re-excision? A Nomogram for Close/Positive Margins After Lumpectomy for DCIS.

Anatomic extent of ductal carcinoma in situ (DCIS) may be uncertain in spite of clinical, pathologic, and imaging data.Consequently close/positive margins are common with lumpectomy for DCIS and often lead to a challenge in deciding whether to perform a re-excision or mastectomy. From a single health system, we identified cases of lumpectomy for DCIS with close/positive margins who underwent re-excision for the purpose of constructing a nomogram. In total, 289 patients were available for analysis. The patients were randomly divided into two sets allocating 70% to the modeling and 30% to the validation set.A multivariable logistic regression model was used to estimate the probability of overall positive margin status using multiple clinicopathologic predictors.Nomogram validation included internal tenfold cross-validation, internal bootstrap validation, and external validation for which a concordance index was calculated to assess the external validity. Significant predictors of persistent positive margins from regression modeling included necrosis at diagnosis (non-comedo or comedo); DCIS not associated with calcifications on core biopsy; high-grade DCIS; progesterone receptor positivity; and number of positive margins at initial surgery.When subjected to internal validation, the nomogram achieved an uncorrected concordance index of 0.7332, a tenfold cross-validation concordance index of 0.6795, and a bootstrap-corrected concordance index of 0.6881. External validation yielded an estimated concordance index of 0.7095. Using clinical and pathologic variables from initial diagnosis and surgery for DCIS, this nomogram predicts persistent positive margins with margin re-excision, and may be a valuable tool in surgical decision-making.

Small non-coding RNA profiling in breast cancer: plasma U6 snRNA, miR-451a and miR-548b-5p as novel diagnostic and prognostic biomarkers.

Breast cancer is a leading cause of cancer-related death in women. Most cases are invasive ductal carcinomas of no special type (NST breast carcinomas). In this prospective, multicentric biomarker discovery study, we analyzed the expression of small non-coding RNAs (mainly microRNAs) in plasma by qPCR and evaluated their association with NST breast cancer. Large-scale expression profiling and subsequent validations have been performed in patient and control groups and compared with clinicopathological data. Small nuclear U6 snRNA, miR-548b-5p and miR-451a have been identified as candidate biomarkers. U6 snRNA was remarkably overexpressed in all the validations, miR-548b-5p levels were generally elevated and miR-451a expression was mostly downregulated in breast cancer groups. Combined U6 snRNA/miR-548b-5p signature demonstrated the best diagnostic performance based on the ROC curve analysis with AUC of 0.813, sensitivity 73.1% and specificity 82.6%. There was a trend towards increased expression of both miR-548b-5p and U6 snRNA in more advanced stages. Further, increased miR-548b-5p levels have been partially associated with higher grades, multifocality, Ki-67 positivity, and luminal B rather than luminal A samples. On the other hand, an association has been observed between high miR-451a expression and progesterone receptor positivity, lower grade, unifocal samples, Ki-67-negativity, luminal A rather than luminal B samples as well as improved progression-free survival and overall survival. Our results indicated that U6 snRNA and miR-548b-5p may have pro-oncogenic functions, while miR-451a may act as tumor suppressor in breast cancer.

Conventional Versus Different Hypofractionated Radiotherapy Dosage Schedules in Postmastectomy Advanced Breast Cancer.

Introduction:The standard treatment for advanced breast cancer is surgery consisting of breast-conserving surgery or modified radical mastectomy (MRM) postneoadjuvant chemotherapy followed by adjuvant radiation treatment (RT). Conventionally-fractionated whole breast irradiation has been the standard RT regimen, but recently shorter courses of hypofractionated whole breast or chest wall irradiation have been advocated for patient convenience and reduction in health-care costs and resources. Radiation is delivered through the same technique, but tumors receive a higher dose of radiation per treatment session with hypofractionation.Aim:The aim of the study was to compare different fractionation schedules of radiotherapy in postoperative cancer breast with respect to locoregional control and toxicities.Materials and Methods:One hundred and eighty-eight patients of cancer breast, who received RT between January 2017 and December 2019 were assessed. Since hypofractionation is well documented and established and being practiced in prestigious institutes, we treated the patients as per their choice to receive 10.15 or 25 fractions. 72 patients (Group A) were treated with conventional fractionation to a dose of 50 Gy/25 fractions/5 weeks. Second group of 62 patients (Group B) were given 40.5 Gy/15 fractions/3 weeks and third group of 54 patients (Group C) were treated with 34 Gy/10 fractions/2 weeks. All patients were T3 or more and underwent MRM after neoadjuvant chemotherapy. They were in the age group of 30–65 years. All of them received adjuvant chemotherapy and hormone therapy in case of estrogen/and progesterone receptor positivity and anti-Her2neu target therapy in case of Her2neu positivity. They were assessed for locoregional control and acute and chronic toxicities.Results:Grade 3 and 4 skin toxicity was similar in all three groups. At 6 months postcompletion of RT, two patients in Group A, 3 in Group B, and 5 in Group C lost to follow-up. In rest of the subjects, there was no locoregional failure. At 1 year, 1 patient from Group A, 2 from Group B, and 1 from Group C developed locoregional recurrence. There were no major chronic toxicities. Arm edema and Telangiectasia were similar in three groups. No rib fracture or major cardiotoxicity and pulmonary toxicity was seen.Conclusion:Hypofractionated RT is a part of the typical treatment regimen for breast cancer nowadays. The major advantage is of convenience to the patients as it is completed the full course of RT in fewer sessions. With both conventional and hypofractionated radiation, the patient receives radiation 5 days a week. In the conventional regimen, though the schedule lasts for 5 weeks, whereas hypofractionation therapy is completed in 2 to 3 weeks. Local control wise both conventional and hypofractionated regimen is similar in locoregional control and toxicity. Therefore, hypofractionated RT should be practiced in cancer breast as it is economical, convenient, and toxicity wise and result wise similar to conventional radiotherapy.

Study of ER, PR and VEGF Expression in Endometrial Epithelial Neoplasms and its Association with Histological Stage and Grade of Endometrial Carcinoma

Introduction: Exogenous or endogenous estrogen induces hyperplastic endometrium which presents with abnormal uterine bleeding. Atypical endometrial hyperplasia is the precursor for endometrial carcinoma. In case of invasive carcinoma, Rstrogen Receptor (ER) and Progesterone Receptor (PR) expressions are commonly diminished but their expressions are generally increased in high grade and high stage endometrial carcinomas. Vascular Endothelial Growth Factor (VEGF), a crucial promoter of angiogenesis in endometrial carcinogenesis, is associated with poor prognosis. This study is needed for assessment of biological behaviour of endometrial epithelial neoplasms and application of targeted antiangiogenic therapy. Aim: 1. Immunohistochemical expression of ER, PR, and VEGF in normal endometrium, hyperplastic endometrium and endometrial carcinoma. 2. Association of the changes in immunohistochemical expression with grade and stage of endometrial carcinoma. Materials and Methods: The present cross-sectional, non interventional, retrospective study was conducted in the Department of Pathology along with Department of Obstetrics and Gynaecology of N R S Medical College, Kolkata, from 1st January 2018 to 30th June 2019 comprising of 51 cases. In the present study, histopathological diagnosis was made for each endometrial lesion with grading and staging of endometrial carcinoma followed by immunohistochemical evaluation, performed on the representative sections using monoclonal antibody. Chi-square test and Z-test were used to observe the association of different study variables and to see the significant difference between two proportions. The p value of&lt;0.05 was taken as statistically significant. Results: Out of 51endometrial samples, eight cases had proliferative endometrium, 14 cases had endometrial hyperplasia without atypia, five cases had atypical endometrial hyperplasia and 24 cases had endometrial carcinoma. ER and PR expression was seen less in endometrial hyperplasia and endometrial carcinoma than in benign proliferative endometrium and there was statistically significant association present between PR expression and histopathological diagnosis. All cases of grade-1 endometrial carcinoma showed ER and PR positivity and decreasing expression in higher grades-2 and 3, but were not statistically significant. Expression of VEGF in the groups of endometrial carcinoma (91.7%) and atypical hyperplasia (80%) was significantly increased in comparison with the groups of normal proliferative endometrium (37.5%) showing a significant statistical association. VEGF expression had no statistical association with grade and stage of endometrial carcinoma. Conclusion: ER, PR and VEGF were effectively associated with prognosis in patients with endometrial carcinoma.

Pleomorphic hyalinizing angiectatic tumor of the vulva: literature review based on a rare presentation.

ABSTRACTPleomorphic hyalinizing angiectatic tumor (PHAT) of soft tissues is a rare, non-metastatic tumor of unknown etiology and uncertain behavior, which may recur locally. There are few reports on this condition, and due to the rarity of the disease, its lineage has not yet been fully elucidated. The present study aims to report the case of an unusual entity observed for the first time in vulval topography. A female patient, 83 years old, presented with a tumor in the vulvar region that had evolved for approximately 4 months. Magnetic resonance imaging showed an expansive perineal formation of 8.5 × 3.5 cm, and a hemivulvectomy with a flap rotation was performed. The review of the slides revealed a mesenchymal lesion without significant atypia, which was richly vascularized. In the areas of interest, the immunohistochemical (IHC) study demonstrated positivity for CD34, estrogen, and progesterone receptors; it was negative for the other tested markers. Morphological findings associated with the IHC staining panel supported the diagnosis of PHAT. The main morphological features of PHAT are clusters of ectatic vessels of different sizes that show deposits of subendothelial and intraluminal fibrin. Fusiform and pleomorphic cells randomly arranged in leaves or long fascicles intermingle these vessels. It is essential to recognize this entity and consider it among the differential diagnoses of a mesenchymal lesion, given the wide variety of entities that comprise this group of lesions.

Mixed Epithelial and Stromal Tumor Family of Kidney (Adult Cystic Nephroma, Mixed Epithelial and Stromal Tumor): Retrospective Clinicopathological Evaluation.

Tumors belonging to the mixed epithelial stromal tumor family (MESTF) are rare; thus clinicopathological experience about them are limited. Each epithelial and stromal component shows different patterns in these tumors. Clinicopathological features of 11 MESTF cases that were diagnosed between 2000 and 2021 at a single center were evaluated. Ten of the 11 patients were female (F:M = 10:1). The mean age of the females was 47 (31-63) years; the male patient was 45 years old. The mean tumor diameter was 6.7 (3.5-19) cm. All tumors had varying proportions of cystic and solid components. Eight cases were well circumscribed, and the others had distinct but irregular borders. Two of the tumors with irregular borders were bulging into the renal sinus. The epithelial component was dominant in most cases. In the epithelial component, macrocyst, microcyst, and tubules were the most common patterns and the most common types of lining epithelium were flat, cuboidal and hobnail. The stromal component was variable in most cases and included hypocellular (mostly collagenous) and cellular areas. In most cases, the cellular stroma had an ovarian-like appearance. Among the other features observed, hyalinization and dystrophic calcification were common. The positivity for estrogen and progesterone receptor in the stromal component was observed in almost all female cases. MESTF, which has distinctive features, should be considered in the differential diagnosis of cystic kidney tumors.

Influence of progesterone receptor on metastasis and prognosis in breast cancer patients with negative HER-2.

In de novo metastatic breast cancer patients, the site of metastasis and prognosis are related to the molecular subtype of breast cancer. There are few relevant reports to explore the clinicopathological and prognostic characteristics of different single positive hormone receptor subtypes [estrogen receptor (ER)+/progesterone receptor (PR)- and ER-/PR+] of metastatic breast cancer. Using the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2015.We analyzed the metastatic patterns and prognosis of human epidermal growth factor receptor 2 (HER-2)-negative breast cancer patients. Cox analysis was used to analyze the influence of ER+/PR- and ER-/PR+ on the prognosis of patients in different subgroups and the risk factors affecting the prognosis of patients with single hormone receptor positivity. We included 206,187 breast cancer patients, including 7,726 stage IV patients. The loss of ER was a protective factor against bone metastasis (P<0.001) and a risk factor for visceral metastasis (P<0.001). The ER-/PR+ subtype had a similar proportion of de novo metastatic breast cancer, and similar clinicopathological characteristics, prognosis with triple negative breast cancer (TNBC). Single PR positivity was an independent risk factor for cancer specific survival (CSS) in multi-visceral metastasis subgroup comparing to TNBC. Meanwhile, no significant difference in overall survival (OS) or breast cancer specific survival (BCSS) between ER-/PR+ and ER-/PR- patients in all breast cancer patients or in stage IV breast cancer patients. Age [hazard ratio (HR) =2.16], grade (HR =2.36), T stage (T4: HR =3.24), lymph node metastasis (>10: HR =4.33), distant metastasis (HR =4.99), and no chemotherapy or an unknown (HR =1.65) were high-risk factors but surgery (HR <0.5) were protective factors for CSS in ER-/PR+ patients. ER-/PR+ subtype had a high proportion of stage IV patients. Meanwhile, such subtype breast cancer had similar clinicopathological characteristics, metastatic models (prefers to visceral metastasis), similar even worse prognosis compared with TNBC.