Maimone, Santo

Abstract Background Metaplastic breast cancer (MBC) is a rare and aggressive subtype of breast cancer (BC) defined by presence of both epithelial and mesenchymal components. Most are triple negative but are often chemo-refractory and associated with poor survival outcomes compared to non-metaplastic triple negative BC. Advances in therapy have led to improvements in survival outcomes of patients (pts) with BC over the last decade. Our multicenter retrospective study aims to assess (1) progression free survival (PFS) and overall survival (OS) (2) factors predictive of survival outcomes in MBC pts Methods We performed a retrospective analysis of pts diagnosed with MBC from 1997-2021 at Mayo Clinic (Florida, Arizona and Rochester) under IRB approval. Kaplan-Meier method was used to estimate OS and PFS at 1, 3 and 5 years. Cox regression models were used to examine the association between risk factors and survival outcomes. All tests were two-sided with p value < 0.05 considered statistically significant Results We evaluated 158 pts with MBC. Median age and tumor size was 61 (range: 20-91) years and 2.8 (range: 0.5-21) cm, respectively, with 80% of pts being postmenopausal. At diagnosis, 14.6% of pts had clinical T3/T4 disease, 16.4% were clinically node-positive, and 6.3% (10 pts) had distant metastases (DM). Spindle cell histology was seen in 36 pts. Most MBC pts were triple-negative (68.3%), high grade (77.2%) and high Ki-67 (36/47; 76.5%). Of the 61 pts tested for germline mutation, 8 (13.1%) were positive, with BRCA1/2, PTEN, NBN, CHEK2, and BARD1 mutations. Most pts had lumpectomy (53.8%), followed by simple mastectomy (38.5), and modified radical mastectomy (7.7%). Majority of pts had sentinel lymph node biopsy (71.8%). Adjuvant radiation therapy was performed in 65.6% of pts. Pathologic complete response (pCR) was noted in 4/38 (10.5%) evaluable pts who received neoadjuvant chemotherapy (NACT). Residual cancer burden (RCB) scores of 2 and 3 were seen in 76.2% of evaluable pts. Median follow-up time was 2.2 years (range: 6 days-24.6 years). Overall, 1-, 3-, and 5-year OS was 93.3%, 81.7%, and 76.0%, while PFS was 80.8%, 67.9%, and 60.9%, respectively. The presence of DM at diagnosis [HR 38.55 (11.18, 132.93), p < 0.001] and spindle cell histology (SC) [HR 2.57 (1.19, 5.53), p = 0.02] predicted worse OS in multivariable analysis. Inferior PFS was predicted by DM [HR 18.84 (6.53, 54.35), p < 0.001], SC [HR 2.46 (1.25, 4.86), p = 0.009], and node-positivity at diagnosis [HR 3.65 (1.5, 8.89), p = 0.004]. The 5-year OS and PFS were 22.2% and 0% for DM pts versus 80.0% and 65.6% for non-DM pts. The 5-year OS and PFS were 71.5% and 54.7% for SC pts versus 81% and 66.6% for non-SC pts. 5-year OS and PFS for NACT pts was 67.3% and 52.6% for NACT pts versus 78.2% and 62.8% for non-NACT pts. Age at diagnosis, menopausal status, family history of BC, grade, stage, tumor size, hormone-receptor and HER2 status, and use of NACT were not found to be significantly associated with OS or PFS in multivariate analysis. Conclusion This study is one of the largest and most recent review of institutional experiences with MBC. Overall, OS at 5 years was improved compared to prior older studies of MBC but still remains very low for those with DM, representing an area of unmet clinical need. SC and DM correlated with worse outcomes for both PFS and OS. Additionally, node positivity at diagnosis was a predictor of worse PFS. In contrast, no association was seen between survival and tumor size, stage, hormone receptor-positivity, HER2 receptor-positivity. The low pCR rates following NACT in our study are consistent with reported literature. Further, use of NACT does not impact survival, suggesting pts with resectable disease should proceed with surgery first. Citation Format: Siven Chinniah, Raza Zarrar, Zhuo Li, Kostandinos Sideras, Alvaro Moreno-Aspitia, Saranya Chumsri, Rohit Rao, Sarah McLaughlin, James Jakub, Emmanuel Gabriel, Sanjay Bagaria, Laura Vallow, Santo Maimone, Pooja Advani. Clinical Factors associated with Survival Outcomes in Patients with Metaplastic Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-25.

AbstractAdvances have dated the genetic testing initially offered to evaluate for hereditary breast and ovarian cancer risks. Previous research has demonstrated that many patients have not updated testing. This study reviewed the incidence of additional analysis after an uninformative BRCA1/2 result and offered updated testing with limited barriers to those who had not completed. After viewing an educational video and providing informed consent, eligible patients were mailed a saliva collection kit to complete an 84‐gene hereditary cancer panel at no personal cost. A total of 704 patients had completed BRCA1/2 only testing between 2001 and 2020. Fifteen percent (N = 102) of the 671 patients with an uninformative BRCA1/2 result had already completed expanded testing. Most, 74 of 102 (73%), had been rereferred to medical genetics during a clinical visit related to cancer care. Those who had already completed additional testing were more likely to have a personal history of cancer (92% vs. 79%, p = 0.002) and live locally (p = 0.032). Invitation to complete updated testing through this study was sent to 372 people, and 116 (31%) consented to participate. For 142 of the 256 who did not proceed with testing through the study, proof of receipt of research information was available. In total, 22 pathogenic variants were reported in 21 of the 226 patients with updated testing from before and including our study: ATM (4), CHEK2 (4), LZTR1 (1), MUTYH (3), NBN (1), NF1 (1), NTHL1 (1), PALB2 (4), PMS2 (1), RAD50 (1), and SPINK1 (1). Many potential barriers of retesting were eliminated by removing personal costs or travel requirements. Still, only about 30% of patients agreed to participate, and a significant portion elected not to proceed. Future research could focus on the discovery of other factors that dissuade patients and what measures may better inform them on potential benefits.

Abstract Objective Establish a radiologist-run consultation clinic to review breast density and supplemental screening exams (SSEs) directly with patients in response to breast density reporting laws. Methods Breast radiologists opened and staffed a clinic for formal patient consultations regarding breast density and SSEs. An IRB-approved questionnaire assessed patient knowledge of breast density, SSEs, and encounter satisfaction. Comparative statistical analyses were performed on knowledge-based questions. Results From February 2019 to February 2021, 294 reimbursable consultations were performed with 215 patients completing pre- and post-consultation questionnaires (survey response rate, 73%). Median patient age was 58 years (range, 34–86 years) and 9% (19/210) had a personal history of breast cancer. An increase in patient knowledge of breast density and SSEs was observed as follows: breast density categories (9% correct pre-consultation (20/215), 86% correct post-consultation (185/215), P < 0.001), dense breast effects on cancer risk (39% correct pre-consultation (83/215), 84% post-consultation (180/215)), mammogram sensitivity (90% correct pre-consultation (193/215), 94% post-consultation (201/215)), and increased cancer detection with SSEs (82% correct pre-consultation (177/215), 95% post-consultation (205/215)) (P < 0.001). Post-consultation, 96% (200/209) were satisfied with the usefulness of information, 89% (186/209) strongly agreed they had sufficient knowledge of SSEs, and 81% (167/205) agreed they would like future opportunities to meet with a breast radiologist. Conclusion A consultation clinic staffed by breast radiologists focused on breast density and supplemental breast cancer screening can provide personalized patient counseling, engage patients in shared decision making, assist referring clinicians, and support high quality patient-centered care.

Abstract Objective Molecular breast imaging (MBI) is a supplemental screening modality consistently demonstrating incremental cancer detection over mammography alone; however, its lengthy duration may limit widespread utilization. The study purpose was to assess feasibility of an abbreviated MBI protocol, providing readers with mediolateral oblique (MLO) projections only and assessing performance in lesion detection and localization. Methods Retrospective IRB-exempt blinded reader study administered to 5 fellowship-trained breast imaging radiologists. Independent reads performed for 124 screening MBI cases, half abnormal and half negative/normal. Readers determined whether an abnormality was present, side of abnormality, and location of abnormality (medial/lateral). Abnormal cases had confirmatory biopsy or surgical pathology; normal cases had imaging follow-up ensuring true negative results. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated to assess performance. A false negative result indicated that a reader failed to detect abnormal uptake; a false positive result indicated a reader incorrectly called an abnormality for a negative case. Tests for association included chi-square, Fisher-exact, and analysis of variance. Results Mean reader performance for detecting abnormal uptake: sensitivity 96.8%, specificity 98.7%, PPV 98.8%, and NPV 96.9%. Accuracy in localizing lesions to the medial or lateral breast was 100%. There were no associations in reader performance with reader experience, reader technique, lesion morphology, or lesion pathology. Median lesion size was 1.0 cm (range: 0.4–8.0 cm). All readers correctly identified 97.7% (42/43) of lesions with malignant or elevated risk pathology. Conclusion An abbreviated MBI protocol (MLO images only) maintained high accuracy in lesion detection and localization.

Abstract Background: This study reports incidence, timing, characteristics, and surveillance imaging of mammographic axillary adenopathy following COVID-19 vaccination. As COVID-19 immunizations continue, with possible booster vaccines upcoming, this study offers timing considerations and potential follow-up recommendations for breast imaging after vaccination. Methods: Retrospective analysis of patients (pts) who received at least one COVID-19 vaccine prior to screening (SM) or diagnostic mammography (DM) at Mayo Clinic Florida between January 15 to May 31, 2021. Vaccine-related information was queried by mammography technologists. Adenopathy was assessed by interpreting radiologists and follow-up studies were collated. Mammogram adenopathy included single enlarged node, multiple enlarged nodes, and adenopathy with soft tissue stranding. Ultrasound adenopathy included mildly prominent nodes with preserved fatty hila to rounded nodes with apparent loss of a fatty hilum. Wilcoxon rank-sum test and Fisher’s exact test were used to compare continuous and categorical variables, respectively. Multivariable logistic regression model was used to evaluate the association between days from vaccine and adenopathy. Results: Of 2349 pts, 34 (1.4%) had adenopathy (DM=6; SM=28) and 3 (0.1%) were symptomatic. Presence of axillary symptoms was associated with abnormal imaging (p<0.001) with an odds ratio of 33 in multivariable model. Median time after vaccine for pts with adenopathy was significantly shorter at 14 days compared to 33 days for pts without adenopathy (p<0.001). Incidence of adenopathy decreased as days from vaccine increased (3.4% for 0-14 days, 2.1% for 15-28 days, and 0.4% for > 28 days, p<0.001). After adjusting for being symptomatic, days from vaccine still had a significant impact on finding mammographic adenopathy (for each day after vaccine, OR=0.96, p<0.001). No significant difference was seen based on age (p=0.66), vaccine brand (p=0.66), vaccine dose (p=0.18). ROC analysis to identify a cutoff value for presence/absence of adenopathy was 0.74 (95% CI 0.67-0.81) at 22.5 days following vaccination. Additional imaging with mammogram and/or ultrasound was requested for 31 pts. These included no follow-up (n=4, 12.9%), repeat ultrasound with or without mammogram in 1-3 months (n=26, 83.9%), and biopsy (n=1, 3.2%, pt with ipsilateral breast cancer with negative results, presumably vaccine induced). To date, all pts who underwent surveillance imaging demonstrated normalization of lymph node appearance. The median time for abnormal imaging related to adenopathy to return to BI-RADS 1 or 2 was 84 (range 13-157) days. Conclusion: The incidence of COVID-19 vaccine-induced adenopathy in this study (1.4%) appeared to be lower than self-reported axillary swelling in COVID-19 vaccine trials (16%) but is still higher than the reported incidence of adenopathy on an otherwise normal SM (0.02-0.04%). The incidence of adenopathy decreased significantly over time and was not present in most pts 28 days after the vaccine. In patients with abnormal adenopathy, followup imaging showed resolution of vaccine-induced adenopathy in most patients by 3 months. Adenopathy(N=34)No Adenopathy (N=2315)P valueAge0.66N342314Median (Range)63.5 (35.0, 83.0)64.0 (30.0, 94.0)Q1, Q351.5, 72.555.0, 71.0Exam type<0.001DM6 (13.3%)39 (86.7%)SM28 (1.2%)2276 (98.8%)Symptomatic<0.001Missing032Yes3 (23.1%)10 (76.9%)No31 (1.3%)2273 (98.7%)Vaccine brand0.66Missing119mRNA-127319 (1.7%)1117 (98.3%)BNT162b214 (1.2%)1138 (98.8%)Other0 (0.0%)41 (100.0%)Vaccine dose0.18Missing0181st9 (2.2%)409 (97.8%)2nd25 (1.3%)1888 (98.7%)Days from vaccine<0.001Median (Range)14.0 (1.0, 91.0)33.0 (0.0, 239.0)Q1, Q38.2, 20.816.0, 61.0Days from Vaccine<0.0010-1418 (3.4%)519 (96.6%)15-2811 (2.1%)513 (97.9%)>285 (0.4%)1283 (99.6%) Citation Format: Kristin Robinson, Santo Maimone, Pooja P Advani, Zhuo Li, Denise Gococo-Benore, Neda Qosja, Ashita Mummareddy, Ahmed M Ashai, Annamaria Wilhelm, Robert Maxwell, Martha Wasserman, Neema Patel, Andrey Morozov, Saranya Chumsri. Incidence and time to resolution of axillary adenopathy on mammography after COVID-19 vaccination [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 P3-03-19.

Abstract Objective Image-guided breast biopsies are safe, efficient, and reliable. However, patients are often anxious about these procedures, particularly those who have never undergone a prior biopsy. Methods This prospective IRB-approved study surveyed 163 patients undergoing their first breast biopsy. Participants provided informed consent and completed a short written survey prior to and immediately after their procedure. Level of anxiety as well as anticipated and actual levels of pain prior to and following the procedure were assessed using a 0–10-point Likert scale. Correlation, bivariate, and regression analyses were performed. Results Regarding the biopsy experience, 133/163 (81.6%) of patients reported it as better than expected. Anxiety decreased significantly from a prebiopsy mean score of 5.52 to a postbiopsy mean score of 2.25 (P < 0.001). Average and greatest pain experienced during the procedure had mean scores of 2.03 and 2.77, respectively, both significantly lower compared to preprocedural expectation (mean 4.53) (P < 0.001). Lower pain scores were reported in US-guided procedures compared to stereotactic- and MRI-guided biopsies (P < 0.001). No significant differences in pain scores were seen in those undergoing single versus multiple biopsies, or when benign, elevated-risk, or malignant lesions were sampled. Positive correlations were seen with prebiopsy anxiety levels and procedural pain as well as with anticipated pain and actual procedural pain. Conclusion Image-guided biopsies are often better tolerated by patients than anticipated. We stress the benefit of conveying this information to patients prior to biopsy, as decreased anxiety correlates with lower levels of pain experienced during the procedure.

Abstract Objective Parenchymal breast cysts are considered to be rare in men and are sparsely described in the literature. The purpose of this study was to review our institution’s experience with male breast cysts in an effort to improve overall understanding and management of this rare entity. Methods An institutional review board–exempt retrospective study was performed. Radiology reports for males who underwent mammogram and/or breast ultrasound at any of our institution’s primary or satellite locations from January 1995 to January 2020 were screened to find males with breast cysts. If cysts were reported and images were available, case review was performed to confirm parenchymal breast cyst(s) and patient characteristics were collated. Results Of 5425 male cases presenting for breast imaging, 19 (0.4%) cases of male breast cysts were confirmed, with a mean patient age of 41.6 years (range: 2–81 years). The most common indication leading to cyst discovery was a palpable lump, corresponding to the site of the cyst in 5 (26.3%) patients and near the site where cyst(s) were ultimately discovered in 7 (36.8%) patients. There were 8 (42.1%) instances of cysts without concurrent gynecomastia. Three (15.8%) men underwent needle sampling. There were no cases of atypia or malignancy on needle biopsy or on subsequent clinical follow-up, with median clinical follow-up of 70.3 months (range: 3.3–259.4 months). Conclusion Male breast parenchymal cysts are rare, but their prevalence is likely underestimated. If detected incidentally or upon targeted evaluation, biopsy may be averted if classic benign cyst features are identified.