Premenopausal Status Research Articles

Plasma fibrinogen acts as a predictive factor for pathological complete response to neoadjuvant chemotherapy in breast cancer: a retrospective study of 1004 Chinese breast cancer patients

BackgroundThe aim of this study was to evaluate the relationship between pre-treatment plasma fibrinogen (Fib) level and pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients and to assess the role of plasma Fib as a predictive factor.MethodsData from 1004 consecutive patients with invasive breast cancer who received NAC and subsequent surgery were retrospectively analysed. Both univariate and multivariate analyses based on logistic regression model were performed to identify clinicopathological factors associated with pCR to NAC. Cox regression model was used to determine the correlation between clinical or pathological parameters and recurrence-free survival (RFS). The Kaplan-Meier method and the log-rank test were applied in the survival analysis.ResultsThe median value of Fib, rather than other plasma coagulation parameters, was significantly increased in non-pCR patients compared with pCR patients (P = 0.002). Based on the cut-off value estimated by the receiver operating characteristic (ROC) curve analysis, patients were divided into low or high Fib groups (Fib < 3.435 g/L or ≥ 3.435 g/L). Low Fib levels were significantly associated with premenopausal or perimenopausal status (P < 0.001), tumour size ≤5 cm (P = 0.002), and positive hormone receptor status (P = 0.002). After adjusted for other clinicopathological factors in the multivariate logistic regression model, low Fib status was strongly associated with pCR to NAC (OR = 3.038, 95% CI 1.667–5.537, P < 0.001). Survival analysis showed that patients with low Fib levels exhibited better 3-year RFS compared with patients with high Fib levels in the tumour size>5 cm group (77.5% vs 58.4%, log-rank, P = 0.0168).ConclusionsThis study demonstrates that low pre-treatment plasma Fib (Fib < 3.435 g/L) is an independent predictive factor for pCR to NAC in breast cancer patients. Moreover, T3-featured breast cancer patients with lower Fib level exhibit better RFS outcomes after NAC compared with high Fib status.

Long-term results of fluorescence and indigo carmine blue dye-navigated sentinel lymph node biopsy.

Sentinel lymph node biopsy is widely applied for the management of clinically node-negative breast cancer, and a radioisotope with a blue dye are most often used as tracers. Fluorescence of indocyanine green could also potentially be used as tracer. This study aimed to demonstrate the long-term survival results of fluorescence-guided sentinel lymph node biopsy. Patients with clinically node-negative breast cancer who underwent surgery as initial treatment were included in this study. Both fluorescence of indocyanine green and indigo carmine blue dye were used as tracers. Axillary lymph node dissection was omitted unless metastasis was pathologically proven in sentinel nodes. Breast cancer recurrence and death were recorded and prognostic factors were identified using disease-free survival and overall survival data. A total of 565 patients were analyzed. There were 14 (2.5%) patients whose sentinel nodes could not be identified, yielding an identification rate of 97.5%. Axillary dissection was performed in 90 patients. Forty-three recurrences including 6 ipsilateral axilla recurrence and 13 deaths were observed during the median 83months of follow-up period. Seven-year disease-free and overall survival were 92.4% and 97.3%, respectively. Multivariate analyses demonstrated that pre-menopausal status and invasive lobular carcinoma were significant unfavorable prognostic factors of disease-free survival. Half of ipsilateral axilla recurrences occurred within 5years after surgery and these recurrences were correlated with inappropriate adjuvant therapy. Fluorescence-guided sentinel lymph node biopsy demonstrated favorable prognostic results and could be alternative to the radioisotope for clinically node-negative breast cancer.

The Clinical and Pathological Profile of BRCA1 Gene Methylated Breast Cancer Women: A Meta-Analysis.

Simple SummaryThe aim of the present meta-analysis was to analyze all available studies reporting clinical characteristics of breast cancer gene 1 (BRCA1) gene hypermethylated breast cancer in women, and to pool the results in order to provide a unique clinical profile of this cancer setting population. Identifying the clinical profile of breast cancer in women harboring BRCA1 gene hypermethylation may help oncologists select a subgroup of patients who may be candidates for BRCA1 methylation assessment, thus, possibly enlarging the cancer population who may benefit from new target-therapy agents. Results showed that BRCA1 gene hypermethylation should be suspected in all breast cancer patients with advanced disease stages, positive lymph nodes, and premenopausal age at diagnosis. Multidisciplinary groups treating women with breast cancer should take into account the possibility of addressing patients with these characteristics with a BRCA1 gene methylation status analysis.Background: DNA aberrant hypermethylation is the major cause of transcriptional silencing of the breast cancer gene 1 (BRCA1) gene in sporadic breast cancer patients. The aim of the present meta-analysis was to analyze all available studies reporting clinical characteristics of BRCA1 gene hypermethylated breast cancer in women, and to pool the results to provide a unique clinical profile of this cancer population. Methods: On September 2020, a systematic literature search was performed. Data were retrieved from PubMed, MEDLINE, and Scopus by searching the terms: “BRCA*” AND “methyl*” AND “breast”. All studies evaluating the association between BRCA1 methylation status and breast cancer patients’ clinicopathological features were considered for inclusion. Results: 465 studies were retrieved. Thirty (6.4%) studies including 3985 patients met all selection criteria. The pooled analysis data revealed a significant correlation between BRCA1 gene hypermethylation and advanced breast cancer disease stage (OR = 0.75: 95% CI: 0.58–0.97; p = 0.03, fixed effects model), lymph nodes involvement (OR = 1.22: 95% CI: 1.01–1.48; p = 0.04, fixed effects model), and pre-menopausal status (OR = 1.34: 95% CI: 1.08–1.66; p = 0.008, fixed effects model). No association could be found between BRCA1 hypermethylation and tumor histology (OR = 0.78: 95% CI: 0.59–1.03; p = 0.08, fixed effects model), tumor grading (OR = 0.78: 95% CI :0.46–1.32; p = 0.36, fixed effects model), and breast cancer molecular classification (OR = 1.59: 95% CI: 0.68–3.72; p = 0.29, random effects model). Conclusions: hypermethylation of the BRCA1 gene significantly correlates with advanced breast cancer disease, lymph nodes involvement, and pre-menopausal cancer onset.

EPIDEMIOLOGICAL CHARACTERISTICS OF FEMALE BREAST CANCER PATIENTS OF SAURASTRA REGION OF GUJARAT-A HOSPITAL BASED STUDY

With the increase in adoption of westernization and sedentary life style in low- and middle-income countries like India, there is a significant increase in breast cancer incidence rate. The exact cause of breast cancer is yet unknown and there are limited studies available on the risk factors associated with breast cancer. Thus, this research work is carried out with an aim to study the region-specific contributing risk factors playing role in breast cancer incidence and their prognosis. We also aimed to study rural-urban disparity in risk factors associated with female breast cancer patients of Saurastra region of Gujarat. This Cross Sectional, Single-Centre, Hospital-based study was conducted in Cancer Hospital at Rajkot, Gujarat India. One-to-one In-person interview of total 174 primary breast cancer patients were carried out and details were collected in pre-tested structured questionnaire. Data obtained from the patients were further analysed using Bürkner’s BRMS package (R) interface and SPSS. In our study, majority of patients are from rural background and its subsequent relationship with other relevant parameters is found to be significant (p less than 0.03). The age of patients ranged from 22 to 76 years and the mean age at diagnosis of the breast cancer was 51.5 years. A positive association is observed between risk of breast cancer and BMI for both pre- and post-menopausal rural and urban women. 37% females were having premenopausal status and 62% females were postmenopausal. Out of total postmenopausal patients, 31% had attained late menopause at the age of 51 years, while 13% females had experienced menarche at less than 12 years of age. Our data is first of its kind studying risk factors playing role in breast cancer incidence in Saurashtra region of Gujarat. Even though having limited patients representing the population this region-specific study is useful for cancer projection and to understand treatment modalities.

Real-world evidence from a University Hospital system regarding the uptake of adjuvant pertuzumab and/or neratinib before and after their FDA approval

PurposeAdjuvant pertuzumab and neratinib are independently FDA-approved for treatment of early-stage HER2-positive breast cancer in combination with or following trastuzumab for one year, respectively. Both agents reduce the risk of recurrence; however, the absolute benefit is modest for many patients with added risk of adverse effects. The purpose of this study was to evaluate the clinical use of adjuvant pertuzumab and neratinib in patients with early-stage HER2-positive breast cancer.MethodsPatients diagnosed with stage I–III HER2-positive breast cancer treated with trastuzumab at four University of Colorado Health hospitals between July 2016 and April 2019 were identified. Patient demographics, cancer stage, treatment, and administration of pertuzumab and/or neratinib were obtained.ResultsWe identified a total of 350 patients who received adjuvant trastuzumab for stage I–III HER2-positive breast cancer; 253 (73.1%) had tumors that were ≥ T2 or node-positive disease. The rate of adjuvant pertuzumab use increased following FDA approval; pertuzumab was administered to the majority of patients with node-positive HER2-positive breast cancer. The use of adjuvant pertuzumab was associated with younger age, premenopausal status, and node-positive disease. Rates of administration of adjuvant neratinib were lower, with only 15.2% of patients receiving this therapy within 3 months of completing adjuvant trastuzumab.ConclusionIn our cohort of patients treated within a diverse healthcare network, the majority of patients with node-positive HER2-positive breast cancer received adjuvant pertuzumab following FDA approval. The use of adjuvant neratinib was less common, potentially as a result of adverse effects, prolongation of therapy, previous administration of adjuvant pertuzumab, and modest benefit.

The effect of pelvic pathology on uterine vein diameters

BackgroundTransvaginal ultrasound (TVS) is a sensitive tool for detecting various conditions that contribute to pelvic pain. TVS can be also used to assess blood flow and measure the size of pelvic veins. Pelvic venous congestion (PVC) is characterised by enlargement of the pelvic veins and has been recognised as a cause of chronic pelvic pain. The reference ranges for uterine venous diameter in women with normal pelvic organs have been established, but there is no information regarding the potential effect of pelvic pathology on the uterine venous diameters. The aim of this study was to examine the size of uterine venous plexus in women with evidence of pelvic abnormalities on TVS and to determine whether the reference ranges need to be adjusted in the presence of pelvic pathology.A prospective, observational study was conducted in our gynaecological outpatient clinic. Morphological characteristics of all pelvic abnormalities detected on TVS and their sizes were recorded. The uterine veins were identified and their diameters were measured in all cases. The primary outcome measure was the uterine venous diameter. Regression analyses were performed to determine factors affecting the uterine venous size in women with pelvic pathology.ResultsA total of 1500 women were included into the study, 1014 (67%) of whom were diagnosed with pelvic abnormalities. Women with pelvic pathology had significantly larger uterine venous diameters than women with normal pelvic organs (p < 0.01). Multivariable analysis showed that pre-menopausal status, high parity, presence of fibroids (p < 0.001) and Black ethnicity were all associated with significantly larger uterine vein diameters. Based on these findings modified reference ranges for uterine venous diameters have been designed which could be used for the diagnosis of PVC in women with uterine fibroids.ConclusionsOur findings show that of all pelvic pathology detected on TVS, only fibroids are significantly associated with uterine venous enlargement. Factors known to be associated with enlarged veins in women with normal pelvic organs, namely parity and menopausal status, also apply in patients with pelvic pathology. Future studies of uterine venous circulation should take into account the presence and size of uterine fibroids when assessing women for the signs of PVC.

Abstract PD12-06: Treatment-related amenorrhea with T-DM1 plus pertuzumab (KP) is lower than with docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) in the phase III neoadjuvant KRISTINE trial

Abstract Background: Cytotoxic chemotherapy (CT) in combination with trastuzumab and pertuzumab (HP) is standard of care for patients (pts) diagnosed with HER2-positive early breast cancer (EBC). While highly effective, the toxicity associated with CT is challenging. In KRISTINE/TRIO-021, neoadjuvant T-DM1 was combined with pertuzumab (KP) and compared to standard TCHP. Pts. received six cycles of neoadjuvant treatment followed by adjuvant therapy (KP or HP). Pts. in the KP arm were allowed to receive standard adjuvant CT. Pathologic complete response (pCR) rate was significantly lower with KP versus TCHP and more pts. had disease progression prior to surgery with KP, resulting in a meaningfully lower event-free survival rate vs. the control (85.3% vs 94.2%). However, 3-year invasive disease-free survival was numerically similar in both arms. Neoadjuvant KP demonstrated less toxicity than standard CT, although treatment discontinuation was higher post-surgery. Association of KP and TCHP with treatment-related amenorrhea (TRA) in premenopausal EBC pts. has not been ascertained. Methods: All pts. with premenopausal status at study entry (those not meeting the menopause definition based on National Comprehensive Cancer Network Guidelines v3, 2012) and with menstrual period documented within 3 months of randomization, were independently evaluated for presence or absence of TRA by two reviewers. TRA, a prespecified exploratory endpoint of KRISTINE, was defined as cessation of menstruation for &amp;gt;12 months in the absence of treatment with ovarian suppression or other interventions that can induce amenorrhea. Pts. were followed from the time of study entry through the 3-year follow up period after surgery. For cases with inconsistent determination between the two reviewers, a third reviewer adjudicated. TRA rates were calculated per arm, hormone-receptor (HR) status, adjuvant CT and age group. Proportions were compared by estimating the odds ratio (OR) and the 95% confidence interval. Results: Of 444 pts. enrolled, 205 were excluded based on being post-menopausal per NCCN guidelines. Of 239 pts. remaining, 56 were excluded due to insufficient data. The median age of pts. included was 40 years (range: 22-53) for TCHP and 42.5 (range: 23-52) for KP. TRA was observed in 55% (50/91) of pts. treated with TCHP compared to 30% (28/92) treated with KP (OR=2.79; 95% CI 1.52-5.12). In pts. with HR-positive EBC, TRA occurred in 62% with TCHP vs 35% for KP (OR=2.998; 95% CI 1.44-6.25). In those with HR-negative EBC, TRA was observed in 42% with TCHP vs. 21% with KP (OR=2.77; 95% CI 0.88-8.72). In the KP arm, TRA was observed in 38% (8/21) of pts. treated with standard adjuvant CT vs. 28% (20/71) of those that did not (OR 1.57; 95% CI 0.57-4.36). For women age ≤ 40, the rate of TRA was 38% with TCHP vs. 17% with KP (OR=3.00; 95% CI 1.05-8.60). For those &amp;gt; 40 years, TRA was observed in 74% treated with TCHP vs. 39% of those with KP (OR=4.50; 95% CI 1.88-10.73). Conclusion: The rate of TRA with standard TCHP is nearly double that observed with KP, suggesting that targeted CT with an antibody-drug conjugate regimen is associated with less gonadal toxicity. Rates of TRA are higher in women over the age of 40 for each treatment arm however KP is associated with lower rate of TRA in each age group. Association of TRA with efficacy outcomes (pCR, iDFS) will be presented. Citation Format: Sara A Hurvitz, Rodrigo Fresco, Karen Afenjar, Daniil Stroyakovskiy, Chiun-Sheng Huang, Hans Wildiers, Kyung Hae Jung, Jean-François Boileau, Mario Campone, Miguel Martín, Vicente Valero, Joseph A. Sparano, W. Fraser Symmans, Peter A. Fasching, Alastair M. Thompson, Nadia Harbeck, Vanesa López-Valverde, Chunyan Song, Thomas Boulet, Eleonora Restuccia, Dennis J. Slamon. Treatment-related amenorrhea with T-DM1 plus pertuzumab (KP) is lower than with docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) in the phase III neoadjuvant KRISTINE trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD12-06.

Abstract PS12-25: Patterns of treatment and outcomes in real world patients with advanced estrogen receptor positive breast cancer receiving palbociclib and endocrine therapy

Abstract Background: Advancement in the treatment of metastatic estrogen receptor positive (ER+) breast cancer has led to the introduction of CDK4/6 inhibitors such as Palbociclib, which are associated with reversal of endocrine resistance and delayed requirement for chemotherapy. Clinical trials to date have demonstrated improved survival outcomes for patients on these agents. The objective of this study was to evaluate their role in a real-world setting. Methods: We performed a retrospective multicentre analysis of patients (pts) with metastatic ER+ breast cancer who were commenced on Palbociclib (PAL) between January 2010 and September 2019. Data extracted included demographics, disease characteristics, treatments, toxicities, response rates and survival outcomes. Statistical analysis was performed using Cox proportional hazard model for univariate analysis and Kaplan Meier curves for survival data. Results: We identified 271 pts. The median age was 60 years (31-88) and 18% (n=48) pts were premenopausal. PAL was combined with the following ET partners: Aromatase inhibitor (AI) (38%, n=103), Fulvestrant (FUL) (38%; n=103), Tamoxifen (4%, n=10), FUL &amp; AI combination (16%, n=44) and other (4%, n=11). Among 71 pts treated in the 1st line, overall response rate (ORR) was 56% (n=40). The median PFS (progression free survival) was 35 months (95% confidence interval [CI], 17.2-52.7) in all pts and 25 months (mo) in those not treated with FUL. In 1st line pts with de novo disease (37%, n=26), there appeared to be a trend towards improved PFS in the FUL vs non FUL group - not reached vs 25 mo (HR 0.21; 95% CI 0.02-1.79, p=0.15). There was no significant difference in PFS between the FUL vs non FUL group in relapsed pts (63%, n=45) treated in the 1st line - 22 vs 20 mo (HR 1.0, 95%CI 0.35-2.9; p=0.96). The median OS was 59 mo (95% CI, 9.5 to 108). Of 74 pts treated in the 2nd line, ORR was 24% (n=18), median PFS was 10 mo (95% CI, 5.8-14.1) &amp; OS was 25 mo (95% CI, 18.3-31.6). Among 126 3rd line pts, ORR was 16% (n=20), median PFS was 5 mo (95% CI, 3.5-6.4) and OS was 20 mo (95% CI, 12.8-27.1). 3 of 9 pts achieved &amp;gt;6 mo of stable disease after switching ET and continuing Palbociclib beyond progression. The most frequent grade 3 toxicities were neutropenia (40%), anaemia (4%), fatigue (3%) &amp; thrombocytopenia (2.5%). The rate of febrile neutropenia was 2.5%. Dose reductions occurred in 40%, with the most common reason being neutropenia. Treatment was discontinued in 3% due to toxicity. Premenopausal status or dose reductions were not associated with poorer survival outcomes. Conclusions: Palbociclib appears to be safe and tolerable in a real-world population and is associated with favourable survival outcomes comparable to that seen in a clinical trial setting. Combining Palbociclib with Fulvestrant as opposed to other endocrine therapies may delay progression in the 1st line setting in patients with de novo metastatic ER+ breast cancer but larger studies are needed to explore this hypothesis further. Citation Format: Lisa Prior, Darko Skrobo, Hazel Murray, Abdul Rehman Farooq, Anne Horgan, Paula Calvert, Emmet Jordan, John McCaffrey, Lillian Smyth, Miriam O'Connor, Michaela Higgins, Desmond Carney, Janice Walshe, Giuseppe Gullo, John Crown, Catherine M Kelly. Patterns of treatment and outcomes in real world patients with advanced estrogen receptor positive breast cancer receiving palbociclib and endocrine therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-25.

Abstract PS6-55: The prognostic utility of AR/ER ratio in young women with breast cancer.

World over, less than a quarter of breast cancer diagnoses are in premenopausal women. However, in India premenopausal women constitute half of all women with breast cancer in most hospital case series. Most of these women present at advanced stages with aggressive subtypes of disease and hence the high mortality.The role and utility of detecting androgen receptor (AR) expression in the different sub-types of breast cancer, especially the ones without hormone receptor expression is yet to be firmly established. Evidence from previous studies is suggestive of its beneficial role in hormone receptor positive (HR+) breast cancer. The biological function of AR on the mammary epithelium is determined by the Estrogen receptor (ER) context, in that, it is found to be anti-proliferative in ER positive tumors while it is thought to promote growth in the absence of ER activity. An interesting approach to representing this interplay is as a ratio between AR/ER expressions. As expected, the ratio has been shown to be positively correlated with better outcomes in hormone receptor cancers, mostly in postmenopausal women. The effect of a high ratio in ER negative tumors seems more complicated. In this study, we have evaluated the AR/ER ratio specifically in patients younger than 50 years in whom the estrogenic influence is dominant due to their premenopausal status. Tumor samples from patients 50 years or younger were chosen from a larger cohort of 275 patients with median follow up of 72 months. Expression of ER and AR proteins were detected by immunohistochemistry (IHC), and the transcript levels of ESR1 and AR were determined by quantitative PCR. Relative normalized units of their gene expression were used to calculate the AR/ER ratio. A cut-off at the 3rd quartile was used to divide tumors into categories of high and low ratios. Clinical characteristics were compared between the low and high ratio groups along with IHC subtype distribution (HR+, HER2+ and Triple negative (TNBC)). Kaplan Meier curves was used for survival analysis and Cox proportional hazard analysis model was used to calculate the hazard ratio (HR). The results were validated in METABRIC dataset. Eighty-eight (32%) patients were <50 years with a mean age of 43 years. AR/ER ratio ranged between 0.6 to 3.5 with a mean of 1.5. Sixty-six tumors were categorized as low and 22 were high based on the 3Q cut off (1.7). Clinical characters such as age, tumor size, grade, stage of disease was not different between the high and low ratio categories. Distribution of IHC subtypes among each group showed high ratio category had 64% TNBC tumors (p<0.0001). Tumors with high ratio had poor disease-free survival, (HR-2.6(95% CI-1-6.9) p-0.03). Trends in the METABRIC dataset was similar with 411(21%) patients <50 years. Ninety-seven patients with high ratio had significantly poor disease-free survival (HR-1.95 (95% CI-1.3-2.7) p-0.000). Interaction between AR and ER is known to influence the AR activity and our results reiterate prognostic ability of AR/ER ratio even in young patients of breast cancer. Our results suggest androgenic influences on clinical progression of breast cancer in this age group mediated through AR, has to be examined by its level in relation to the activity of ER, particularly in hormone receptor negative breast cancers. Even more importantly, examining these influences in the context of the menopausal status might help identify subgroups of patients most likely to benefit from interventions targeted at AR.

Abstract PS13-19: Achieving a pathologically negative axilla after neoadjuvant chemotherapy for breast cancer is associated with presenting tumor size and subtype

Abstract Introduction: Axillary pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) confers higher overall and recurrence-free survival, compared to residual axillary disease. Recent findings suggest that pCR in the breast (ypT0) post-NAC is associated with a pathologically negative axilla (ypN0) in patients (pts) presenting with lower stage HER2+ and triple negative breast cancer (TNBC). Additional studies are needed to understand how clinical T (cT) and N (cN) staging are associated with ypN0 in other tumor subtypes, including hormone-receptor (HR) positive tumors. The ability to reliably predict axillary pathologic response post-NAC may allow identification of a subset of pts for whom axillary staging may be safely omitted. We hypothesize that tumor subtype and lower clinical stage at presentation are associated with ypN0. Methods: A single institution cancer registry was retrospectively reviewed for pts receiving NAC followed by surgery from January 2010-June 2018. Fisher’s exact tests were used to compared proportion of breast and axillary pCR by tumor subtype (TNBC, HR+/HER2-, HR+/HER2+ and HR-/HER2+). Univariable logistic regression determined factors associated with ypN0. Multivariable logistic regression determined the association between ypN0 and tumor subtype adjusting for factors that retained significance on univariable analysis. Sensitivity analyses determined how cN status affected ypN status by tumor subtype. Results: Of the 1348 pts who received NAC followed by surgery, median age was 54 (IQR 44-63); 59% (n=738) were postmenopausal. Proportion of tumor subtypes were: 15% (n=197) TNBC, 12% (n=155) HR+/HER2-, 48% (n=653) HR+/HER2+, and 25% (n=343) HR-/HER2+. Tumor size at diagnosis was: 1% (n=18) T0, 20% (n=272) T1, 53% (n=713) T2, 17% (n=230) T3 and 9% (n=111) T4. Clinical nodal staging at diagnosis was: 52% cN0 (n=695), 41% cN1 (n=550), 5% cN2 (n=61), and 3% cN3 (n=43). TNBC and HER2+ subtypes were associated with the highest rate of breast pCR and ypN0. On univariable analyses of the cN positive pts, younger age at diagnosis, non-postmenopausal status, oral contraceptive use, alcohol consumption, cT stage, cN stage and tumor subtype were significantly associated with ypN0 (Table1A). In the adjusted model, postmenopausal status, cT, and tumor subtype were associated with ypN0. Lower cT and HR- subtypes had significantly higher odds of ypN0 (Table 1B). In sensitivity analyses, cN2/cN3 was associated with lower odds of ypN0 compared to cN0/cN1 disease in TNBC (OR0.11 95%CI 0.03,0.40, p=0.001), HR-/HER2+ disease (OR0.42, 95%CI 0.22,0.77, p=0.005), and HR+/HER2+ (OR0.26 95%CI 0.11,0.61 p=0.002), but not in HR+/HER2- disease (OR1.17, 95%CI 0.25,5.57, p=0.838). Conclusion: HR- and low cT stage at diagnosis are associated with ypN0 in this large cohort. Younger age, pre-menopausal status and cN stage may be important considerations in future investigations aimed at defining the subset of patients most likely to achieve ypN0 and ultimately to be considered for de-escalation of axillary staging post NAC. A.Univariable logistic regression analysisVariableOdds Ratio95% Confidence Intervalp valueAge at diagnosis0.990.98, 0.99&amp;lt;0.001RaceWhite1.060.70, 1.600.777Black0.600.17, 2.080.421Asian1.200.36, 4.000.768Postmenopausal0.760.60, 0.960.023BMI1.000.99. 1.000.424Oral contraceptive use1.250.95, 1.630.114Alcohol consumption1.601.05, 2.440.027 Tobacco use1.130.99, 1.290.064Family history of cancer1.250.92, 1.680.148Grade12.170.75, 6.250.15320.950.45, 2.010.89131.700.81, 3.590.163HistologyIDC1.451.10, 1.890.007ILC0.370.23, 0.60&amp;lt;0.001Mixed0.950.68, 1.320.764Other0.440.18, 1.080.073Clinical T stage11.370.47, 3.980.56920.760.27, 2.160.60530.350.12, 1.020.05540.150.05, 0.450.001Clinical N stage10.140.11, 0.18&amp;lt;0.00120.130.07, 0.23&amp;lt;0.00130.110.06, 0.21&amp;lt;0.001Tumor subtypeTNBC1.591.00, 2.530.049HR+/ HER2 -0.550.35, 0.870.010HR+/ HER2+0.690.47, 1.000.049HR-/ HER2 +1.641.09, 2.460.019B.Multivariable logistic regression analysisAge at diagnosis0.980.97, 0.99&amp;lt;0.001Alcohol use1.190.74, 1.930.476HistologyIDC1.150.82, 1.610.414ILC0.570.32, 1.010.053Mixed1.080.71, 1.630.721Other0.790.28, 2.220.660Clinical T stage11.190.39, 3.580.76120.740.25, 2.160.58530.510.17, 1.540.23540.290.09, 0.910.034Clinical N stage10.130.10, 0.18&amp;lt;0.00120.140.08, 0.26&amp;lt;0.00130.100.05, 0.20&amp;lt;0.001Tumor subtypeTNBC1.440.84, 2.470.181HR+/ HER2 -0.540.31, 0.940.028HR+/ HER2+0.600.39, 0.930.024HR-/ HER2 +1.701.05, 2.730.030 Citation Format: Sara P Myers, Gillian M Ahrendt, Joanna S Lee, Jennifer G Steiman, Atilla Soran, Ronald R Johnson, Priscilla F McAuliffe, Emilia J Diego. Achieving a pathologically negative axilla after neoadjuvant chemotherapy for breast cancer is associated with presenting tumor size and subtype [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-19.

Abstract PS7-65: Triple negative breast cancer prospective registry in middle East and Africa (TRIPOLI) study: Interim analysis of the patients’ characteristics

Abstract Background:Globally, triple-negative breast cancer (TNBC) is responsible for approximately 15% of all invasive Breast cancer and has been typically associated with poor prognosis. Some retrospective studies have suggested a relatively higher incidence of TNBC in the Middle East and North African Arab countries. Nevertheless, there is complete lack of prospective data, on TNBC in the region, including clinico-pathologic characteristics, treatment patterns and disease outcomes. The TRIPOLI study aims to bridge this information gap.Methods:TRIPOLI is an ongoing prospective multinational, disease registry, designed to recruit 700 newly diagnosed TNBC patients, from 15 institutions within 9 Arab countries: Egypt, Jordon, Morocco, Kingdom of Saudi Arabia, Lebanon, Oman, Kuwait, Qatar and Iraq. This interim analysis includes the patients’ characteristics and treatment approaches of the first 449 cases included in the study from December 2017 to September 2019.Results:All the 449 TNBC patients were females, with a median age of 49 years (range 23.8 - 93.6 years). Premenopausal status was reported in 54.7%, while a positive family history of BC was stated in 25.2% of these cases. 0.2% of patients were below normal (BMI&amp;lt;18.5), 17.2% had normal weight (18.5≤BMI&amp;lt;25), and 30.5% were overweight (25≤BMI&amp;lt;30). Obesity (BMI ≥ 30) was present in 52% of these patients, while a parity of ≥3 children was present in 254 patients (59.8%) Sixty-six patients (14.7%) had tumours smaller than 2cm. 159 patients (35.4%) had node negative disease. The majority of patients had invasive duct carcinoma (87.1%) with 5 patients (1.1%) grade I, 181 (40.3%) grade II and 234 (52.1%) grade III tumours (29 (6.5%) had unknown histological grade). Thirty-four patients (7.6%) presented with stage I disease, 203 patients (45.2%) with stage II, 161 patients (35.9%) with stage III and 50 patients (11.1%) presented with stage IV disease.Out of the 387 patients with non-metastatic disease who started treatment, 217 patients (56.1%) had upfront surgery and 170 patients (43.9%) started with neoadjuvant chemotherapy. Compared to patients &amp;gt; 40 years, patients ≤ 40 years were less likely to be obese (39.4% versus 60.6%; p=0.002), more likely to have grade III tumours (62.3% versus 53.5%; p=0.116), more likely to have T3 or T4 tumours (41.4% versus 32.7%; p=0.038).Conclusion:In this interim analysis, Arab women with TNBC had high parity (≥ 3) and high BMI, compared to existing literature based on western population. High tumor grade, younger age and advanced stages at presentation are in line with similar world-wide reports. Younger women in the Arab region (≤40 years) presented with poor prognostic features, which will be further elucidated in subsequent reports. Citation Format: Hamdy A. Azim, Alaa Kandil, Heba El Zawahry, Hikmat Abdel-Razeq, Hesham Elghazaly, Suad Al Kharusi, Manal M. Abdelwahab, Salah Fayaz, Ahmed Saadeddin, Huda A. Alabdulkarim, Rasha Aboelhassan, Hassan Errihani, Tahseen Al Rubai, Salha Bujassoum Al Bader, Nashwa Mohamed Abdel Aziz, Nagi El Saghir, Giulia Attinà, Ahmed Yosry, Mohamed El Leithy, Loay Kassem, Marwan Ghosn. Triple negative breast cancer prospective registry in middle East and Africa (TRIPOLI) study: Interim analysis of the patients’ characteristics [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-65.

Abstract PS4-30: Neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio as prognostic biomarkers in patients with metastatic breast cancer treated with CDK4/6 inhibitors

Abstract Background: Immune regulation plays an important role in tumor growth and sustainability. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been reported as peripheral blood surrogates of tumor inflammation and immune response, and have been studied as prognostic markers of treatment response in breast cancer. Cyclin-dependent kinase (CDK) 4/6 inhibitors have shown to enhance the immune response against tumor cells. We aimed to evaluate the impact of NLR and PLR as prognostic biomarkers in patients with estrogen-receptor positive (ER+), human-epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (MBC) treated with first line CDK4/6 inhibitors. Methods: This retrospective single cohort study analyzed patients with ER(+)/HER2(-) MBC treated with first line CDK4/6 inhibitors at Albert Einstein Cancer Center. Demographic, clinicopathological, laboratory and treatment characteristics were collected from electronic medical records. Absolute neutrophil count, absolute lymphocyte count and platelet count, were obtained at baseline (T0) and after three months (T3) of treatment with CDK4/6 inhibitors. Optimal cutoff points to define NLR and PLR high vs. low were identified using time-dependent receiver operator curves. Progression free survival (PFS) was calculated from the time of CDK4/6 inhibitor initiation to disease progression, death, or last clinical encounter. PFS was compared among patients with high vs. low ratios at T0 (NLR0HIGH vs. NLR0LOW and PLR0HIGH vs. PLR0LOW) and at T3 (NLR3HIGH vs. NLR3LOW and PLR3HIGH vs. PLR3LOW) of CDK 4/6 inhibitor treatment, using Cox-proportional regression models. Results: A total of 89 patients were evaluated. The median age was 61 years [interquartile range (IQR): 61-69]. Of these, 60% were Non-Hispanic, 40% were Hispanic, 46% were Black, 19% were Caucasian and 6% were Asian. Premenopausal and postmenopausal status was identified in 21% and 75% of patients, respectively. The median Charlson Comorbidity Index (CCI) was 8 [IQR: 7-9]. Visceral metastases were seen in 67% of patients. Palbociclib, Abemaciclib and Ribociclib were used in 78%, 16% and 7% of patients, respectively; with an endocrine therapy backbone of Letrozole, Fulvestrant and Anastrozole in 64%, 24% and 10% of patients, respectively. The median NLR0 and NLR3 were 2.6 [IQR: 1.8-3.6] and 1.3 [IQR: 0.8-2.3], respectively. The median PLR0 and PLR3 were 158 [IQR: 115-250] and 142 [IQR: 94-290], respectively. The cutoff points for defining ratios as being high vs. low for NLR0, NLR3, PLR0, and PLR3 were 3.7, 2.2, 108, and 309, respectively. The median PFS was 10 vs. 19 months for NLR0HIGH vs. NLR0LOW [Hazard Ratio (HR):1.8, 95% Confidence Interval (CI):0.95-3.49, p=0.07] and 12 vs. 19 months for NLR3HIGH vs. NLR3LOW (HR:1.46, CI:0.71-3.00, p=0.3). In multivariable models adjusted for age, CCI, and visceral metastases, neither NLR0(p=0.1) nor NLR3 (p=0.2) was associated with PFS. The median PFS was 13 months vs. not-reached for PLR0HIGH vs. PLR0LOW (HR: 5.5, CI:1.3-23.0, p=0.018), and 32 vs. 16 months for PLR3HIGH vs. PLR3LOW (HR:0.62, CI:0.23-1.64, p=0.3). In multivariable models adjusted for age, CCI, and visceral metastases, an increased PLR0 was associated with worse PFS (HR 4.67, 95%CI 1.1-20, p=0.04), while PLR3 was not associated (p=0.37). Conclusions: Our study is the first in the United States to evaluate NLR and PLR as prognostic biomarkers in MBC patients receiving CDK4/6 inhibitors. PLR0 is a potential biomarker for prognostic stratification in this setting. NLR0, NLR3, and PLR3 were not independent factors for PFS in this setting when other clinicopathological factors were considered. Further studies with a larger sample size are required to validate our results. Citation Format: Ashley Weiner, Laura S. Munoz-Arcos, Heidi Ko, Jesus Anampa. Neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio as prognostic biomarkers in patients with metastatic breast cancer treated with CDK4/6 inhibitors [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-30.

Characterization of Oligometastatic Disease in a Real-World Nationwide Cohort of 3447 Patients With de Novo Metastatic Breast Cancer.

BackgroundObservational studies in metastatic breast cancer (MBC) show that long-term overall survival (OS) is associated with limited tumor burden, or oligo-MBC (OMBC). However, a uniform definition of OMBC is lacking. In this real-world nationwide cohort, we aimed to define the optimal OMBC threshold and factors associated with survival in patients with OMBC.Methods3535 patients aged younger than 80 years at diagnosis of de novo MBC in the Netherlands between January 2000 and December 2007 were included. Detailed clinical, therapy, and outcome data were collected from medical records of a sample of the patients. Using inverse-sampling-probability weighting, the analysis cohort (n = 3447) was constructed. We assessed OS according to number of metastases at diagnosis to determine the optimal OMBC threshold. Next, we applied Cox regression models with inverse-sampling-probability weighting to study associations with OS and progression-free survival in OMBC. All statistical tests were 2-sided.ResultsCompared with more than 5 distant metastases, adjusted hazard ratios for OS (with 95% confidence interval [CI] based on robust standard errors) for 1, 2-3, and 4-5 metastases were 0.70 (95% CI = 0.52 to 0.96), 0.63 (95% CI = 0.45 to 0.89), and 0.91 (95% CI = 0.61 to 1.37), respectively. Ten-year OS estimates for patients with no more than 3 vs more than 3 metastases were 14.9% and 3.4% (P < .001). In multivariable analyses, premenopausal andperimenopausal status, absence of lung metastases, and local therapy of metastases (surgery and/or radiotherapy) added to systemic therapy were statistically significantly associated with better OS and progression-free survival in OMBC, independent of local therapy of the primary tumor.ConclusionOMBC defined as MBC limited to 1-3 metastases was associated with favorable OS. In OMBC, local therapy of metastases was associated with better OS, particularly if patients were premenopausal or perimenopausal without lung metastases.

Weight Changes in Women Receiving Chemotherapy for Non-Metastatic Breast Cancer in Saudi Arabia.

BackgroundWomen with breast cancer (BC) commonly experience weight gain during chemotherapy, although there is conflicting evidence regarding the contributing factors. This study aimed to evaluate body weight changes among women undergoing chemotherapy for non-metastatic BC during the first year after diagnosis, and to determine whether baseline body weight and/or hemoglobin concentration values were associated with weight changes during chemotherapy.MethodsThis retrospective study evaluated patients who were treated at the King Abdulaziz University Hospital (Saudi Arabia) during 2010-2019. A total of 228 women were included based on the following criteria: new diagnosed BC, age of 18-80 years, non-metastatic disease, and initial chemotherapy treatment for BC. The patients’ baseline characteristics, including body weight during the first chemotherapy cycle, were collected from their electronic medical records. Each patient’s weight was then followed at each hospital visit until the last chemotherapy cycle. In addition, data were collected regarding tumor status, menopausal status, chemotherapy regimen, hemoglobin concentration, recurrence status, and death.ResultsThe mean patient age was 53.37±10.9 years and 55.7% of the patients were pre-menopausal. The vast majority of patients underwent surgery (96.9%) and most patients received adjuvant chemotherapy (63.6%) or adjuvant radiotherapy (68.9%). The mean number of chemotherapy cycles was 6.29±1.74 (taxane-based: 1.67±1.36 cycles, anthracycline-based: 2.61±1.81 cycles). At the end of chemotherapy, the body weight changes were classified as increased (41.7% of patients, mean increase: 3.39 kg), decreased (35.5% of patients, mean decrease: -4.12 kg), or stable (22.8%). Factors that predicted weight gain after chemotherapy included younger age at diagnosis (p<0.029), pre-menopausal status (p<0.003), and a high number of taxane-based chemotherapy cycles (p<0.029).ConclusionsChemotherapy for BC did not lead to significant changes in body weight among women in Saudi Arabia. Weight gain in this setting was significantly associated with younger age, pre-menopausal status, and a high number of taxane-based chemotherapy cycles.

Development of a predictive model utilizing the neutrophil to lymphocyte ratio to predict neoadjuvant chemotherapy efficacy in early breast cancer patients

Neutrophils and lymphocytes are key regulators of breast cancer (BC) development and progression. Neutrophil to lymphocyte ratio (NLR) values have been found to offer clear prognostic utility when evaluating BC patients. In this study, we sought to determine whether BC patient baseline NLR values are correlated with pathological complete response (pCR) following neoadjuvant chemotherapy (NCT) treatment. In total, 346 BC patients underwent NCT at our hospital from January 1, 2014 to October 31, 2019, and data pertaining to these patients were retrospectively analyzed. Correlations between clinicopathological characteristics and pCR rates were assessed via multivariate logistic regression analyses. A predictive scoring model was used to gauge the likelihood of pCR based upon regression coefficient (β) values for each significant variable identified through these analyses. NLR cut-off values suitable for identifying patients likely to achieve pCR following NCT treatment were calculated using receiver operating characteristic (ROC) curves. All patients in the present study were females with a median age of 48 years old (range 22–77). An optimal NLR cut-off value of 1.695 was identified and was associated with respective sensitivity and specificity values of 63.6% and 45.5%. We found that higher NLR values were significantly associated with younger age, premenopausal status, and non-pCR status. Logistic regression analyses indicated that NLR, tumor size, hormone receptor (HR) status, and Ki-67 expression were all independent predictors of pCR. The area under the curve (AUC) for the resultant predictive scoring model was 0.705, and this model was assessed via K-fold cross-validation (k = 10) and bootstrapping validation, yielding respective AUC values of 0.68 and 0.694. Moreover, the incorporation of NLR into this predictive model incrementally improved its overall prognostic value relative to that of a model not incorporating NLR (AUC = 0.674). BC patients with a lower baseline NLR are more likely to exhibit pCR following NCT treatment, indicating that NLR may be a valuable biomarker for BC patient prognostic evaluation and treatment planning. Overall, our results demonstrate that this NLR-based predictive model can efficiently predict NCT efficacy in early BC patients with a high degree of accuracy.

Menopausal status and observed differences in the gut microbiome in women with and without HIV infection.

Gut microbiota respond to host physiological phenomena, yet little is known regarding shifts in the gut microbiome due to menopausal hormonal and metabolic changes in women. HIV infection impacts menopause and may also cause gut dysbiosis. We therefore sought to determine the association between menopausal status and gut microbiome composition in women with and without HIV. Gut microbiome composition was assessed in stool from 432 women (99 premenopausal HIV+, 71 premenopausal HIV-, 182 postmenopausal HIV+, 80 postmenopausal HIV-) via 16S rRNA gene sequencing. We examined cross-sectional associations of menopause with gut microbiota overall diversity and composition, and taxon and inferred metagenomic pathway abundance. Models were stratified by HIV serostatus and adjusted for age, HIV-related variables, and other potential confounders. Menopause, ie post- versus premenopausal status, was associated with overall microbial composition only in women with HIV (permutational MANOVA of Jensen Shannon Divergence: P = 0.01). In women with HIV, menopause was associated with enrichment of gram-negative order Enterobacteriales, depletion of highly abundant taxa within Prevotella copri, and alterations in other low-abundance taxa. Additionally, menopause in women with HIV was associated with enrichment of metagenomic pathways related to Enterobacteriales, including degradation of amino acids and phenolic compounds, biosynthesis of enterobactin, and energy metabolism pathways. Menopause-related differences in some low-abundance taxa were also observed in women without HIV. A changing gut microbiome may be an overlooked phenomenon of reproductive aging in women with HIV. Longitudinal assessments across all reproductive stages are necessary to confirm these findings and identify health implications.

The Relationship Between Mammographic Density and Factors Affecting Breast Cancer Risk.

Objectives:Although the relationship between breast cancer (BC) risk factors and mammographic density (MD) patterns is not clear, high MD is well known as an independent risk factor for BC. Thus, the aim of this study was to examine the association between MD and BC risk factors in BC patients and find a correlation between MD and tumor characteristics in BC patients.Methods:Our data included 242 patients with BC. Furthermore, the MD (type I - <25%; type II - 25–50%; type III - 51–75%; and type IV - >75%) was categorized according to percentile density, and the various types of MD were compared using risk factors for BC and tumor characteristics of patients.Results:The results of this study indicated that younger age, pre-menopausal status, younger menarche age, nulliparity, low body mass index, and smoking significantly increase the percentage of MD (p<0.001, p<0.001, p=0.04, p<0.001, p=0.003, and p=0.01, respectively). Moreover, the distribution of MD patterns showed significant differences according to tumor subtypes. Type 4 mammographic pattern was higher in patients with human epidermal growth factor receptor 2 (Her2) type of tumor (p=0.01).Conclusion:Higher MD is related to reproductive risk factors and tumor subtypes, especially Her2 type, in BC patients. Further studies are needed to identify the factors related to breast density.

Giant Ovarian Cyst Adenoma in a Postmenopausal Woman: A Case Report with Literature review

Giant ovarian cysts are benign in most cases and histopathologically they are either serous or mucinous. A case of large ovarian cyst (20 × 18 × 10cm) is reported here. She presented at our OPD clinic with complaints of gradual distension of abdomen and a palpable mass for 6 months. At laparotomy a giant, cystic, smooth, vascularized mass adherent with fallopian tube was encountered. Considering age and premenopausal status we performed Total Abdominal Hysterectomy with Bilateral Salphingo-ophorectomy. Histopathology revealed serous cystadenoma of ovary. Post-operative recovery was excellent and patient was discharged at 5th post-operative day in a good health status.

Background parenchymal enhancement on contrast-enhanced spectral mammography does not represent an influencing factor for breast cancer: A preliminary study.

To compare the relationship between background parenchymal enhancement (BPE) on contrast-enhanced spectral mammography (CESM), mammographic breast density (MBD), age, in the group with benign vs malignant breast lesions.Four hundred thirty three non-high-risk patients from January 2018 to May 2019 were retrospectively analyzed. Patients were assigned into 4 groups: premenopausal benign lesions, premenopausal malignant lesions, postmenopausal benign lesions, and postmenopausal malignant lesions. The differences in CESM BPE and MBD between premenopausal benign lesions and premenopausal malignant lesions, between postmenopausal benign lesions and postmenopausal malignant lesions, between premenopausal and postmenopausal benign lesions, and between premenopausal and postmenopausal malignant lesions were evaluated. Pearson Chi-Squared test was used to analyze the differences between the above groups. Spearman rank correlation analysis was used to evaluate the correlations between BPE, MBD, and age. Multiple logistic regression was used to analyze the influencing factors of breast cancer. P < .05 was considered statistically significant.There was no significant difference in CESM BPE or MBD of benign and malignant lesions regardless of premenopausal or postmenopausal status, but there was a significant difference in CESM BPE and MBD of premenopausal and postmenopausal patients regardless of the presence of benign or malignant lesions. The intensity of CESM BPE was positively correlated with MBD, and the intensity of CESM BPE and MBD were negatively correlated with age. Multiple logistic regression analysis showed that age was an influencing factor for breast cancer in both premenopausal and postmenopausal patients.For non-high-risk women, CESM BPE and MBD were not correlated with benign or malignant breast lesions, and age was an influencing factor for breast cancer.

Factors Associated With Background Parenchymal Enhancement on Contrast-Enhanced Mammography.

OBJECTIVE. The purpose of this study was to determine the relationship between background parenchymal enhancement (BPE) on contrast-enhanced mammography (CEM) and breast tissue density, menstrual status, endocrine therapy, and risk factors for breast cancer and also to evaluate interreader agreement on classification of BPE on CEM. MATERIALS AND METHODS. Five subspecialty-trained breast radiologists independently and blindly graded tissue density (with fatty tissue and scattered fibroglandular tissue classified as nondense tissue and with heterogeneously dense and extremely dense classified as dense tissue) and BPE (with minimal or mild BPE categorized as low BPE and moderate or marked BPE categorized as high BPE) on CEM examinations performed from 2014 to 2018. Electronic medical charts were reviewed for information on menstrual status, endocrine therapy, history of breast surgery, and other risk factors for breast cancer. Comparisons were performed using the Kruskal-Wallis test, Mann-Whitney test, and Spearman rank correlation. Interreader agreement was estimated using the Fleiss kappa test. RESULTS. A total of 202 patients (mean [± SD] age, 54 ± 10 years; range, 25-84 years) underwent CEM. Tissue density was categorized as fatty in two patients (1%), scattered fibroglandular in 67 patients (33%), heterogeneously dense in 117 patients (58%), and extremely dense in 16 patients (8%). Among the 202 patients, BPE was minimal in 77 (38%), mild in 80 (40%), moderate in 31 (15%), and marked in 14 (7%). Dense breasts, younger age, premenopausal status, no history of endocrine therapy, and no history of breast cancer were significantly associated with high BPE. Among premenopausal patients, no association was found between BPE and time from last menstrual period to CEM. Overall interreader agreement on BPE was moderate (κ = 0.41; 95% CI, 0.40-0.42). Interreader agreement on tissue density was substantial (κ = 0.67; 95% CI, 0.66-0.69). CONCLUSION. Women with dense breasts, premenopausal status, and younger age are more likely to have greater BPE. Targeting CEM to the last menstrual period is not indicated.