Rare Subtype Of Breast Cancer Research Articles

Breast conservation versus mastectomy for metaplastic breast cancer: A systematic review and meta-analysis.

Metaplastic breast cancer is a rare aggressive subtype of breast cancer for which there are no clear treatment guidelines regarding the optimal surgical approach. This systematic review and meta-analysis aimed to evaluate survival outcomes of patients with metaplastic breast cancer undergoing breast conservation compared with mastectomy. We identified studies from MEDLINE, Pubmed, EMBASE, Google Scholar, the Cochrane Library Register of Controlled Trials and the EBM Reviews Register. Studies were deemed suitable for inclusion where they compared breast-conserving surgery to mastectomy with the primary outcome of overall survival. Survival data were pooled using a random-effects model. From the 456 citations screened by our search, three studies were assessed as eligible for inclusion. There were a total of 2995 patients who underwent mastectomy and 1909 who underwent breast conservation. The median follow-up time was 43 months. Meta-analysis demonstrated no significant difference between breast conservation and mastectomy (pooled HR 0.89, 95% CI, 0.56-1.42, p=0.631). Wide local excision, in conjunction with adjuvant radiation and judicious use of chemotherapy, may be a reasonable alternative to mastectomy as surgical management of metaplastic breast cancer as part of an individualized, multidisciplinary approach.

Abstract PO5-17-07: MUCINOUS BREAST CARCINOMA: REAL WORLD DATA IN A REFERENCE CENTER IN SÃO PAULO

Abstract BACKGROUND: Mucinous breast carcinoma (MC) is a subtype of invasive carcinoma that corresponds to 1 to 6% of all types of breast cancer. It occurs when the mucinous component accounts for more than 50% of the tumor producing extracellular mucin in large scale. Mucin is a complex carbohydrate engaged in processes such as epithelial differentiation, adhesion modulation and cell signaling. Along with other special types of breast neoplasia, MC appears to have an unique behavior and, since it’s low amount of cases, a detailed clinical evaluation has been difficult. OBJECTIVES: To describe the profile of patients with breast MC that were treated in a reference center in São Paulo, Brazil as well as evaluate its management and outcomes. METHODS: A descriptive longitudinal observation study conducted at São Paulo’s Women’s Health Reference Center - Hospital da Mulher from July 2022 to January 2023, based on 192 medical records of patients diagnosed with MC from 2003 to 2018. RESULTS: 192 patient’s records were included. The age range was 31-93 years, out of which 74,3% of the patients were older than 50 when diagnosed. 48,7% identified as white and 43,7% showed earlier diagnoses of systemic hypertension. The time range between diagnosis and first treatment was 4,5 months. Out of the histopathological features, the nuclear grade was 3 in 69 patients (34,6% of the cases), and histological grade 1 in 52,7%. About pathological staging, the size of the tumors went form 0,5 to 9,5 cm, with an average of ± 4,7cm, the majority of them showed positive ER (89,4%), negative PR (85%), and were negative for Her-2 (76%). Greater number of patients (92,4%) went through both clinical and surgical treatment. Only 15 (7,5%) had isolated clinical treatment. 31% of the patients received systemic chemotherapy treatment, 25% of those were neoadjuvant. 81,9% of patients received aromatase inhibitor and only 17% radiotherapy. Distant metastasis were diagnosed in 27 patients (13,5%) and the local recurrence was observed in 15,3%. Out of distant metastasis, pulmonary type was more prevalent, registered in 45,7% of patients, followed by osseous (22,88%) and hepatic (14,2%). 33 patients (16,5%) progressed to death, however, the specific cause was not determined. CONCLUSION: MC is a rare subtype of breast cancer, more prevalent in post-menopausal and white women. Frequently shows low histological grade and positive hormonal receptors, which reinforces the idea of a indolent behavior. The treatment is mostly surgical, with adjuvance if necessary. Metastasis are infrequent and knowing the profile of patients with MC, as well as it’s behavior, allows the better management when facing this diagnosis. Citation Format: Marina Fleury De Figueiredo, Andre Mattar, Felipe Cavagna, Ana Lígia Minatel da Silva, Rafaella Nadai, Juliana Medeiros de Oliveira, Luma Fleury de Figueiredo. MUCINOUS BREAST CARCINOMA: REAL WORLD DATA IN A REFERENCE CENTER IN SÃO PAULO [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-17-07.

Abstract PO3-20-11: Among the < 0.1 percent of breast cancers: A case of adenoid cystic carcinoma

Abstract Among the < 0.1 percent of breast cancers: A case of adenoid cystic carcinoma Sera Choi, B.A., Sarah Keshwani, M.D., Andrea Madrigrano, M.D. Introduction: Adenoid cystic carcinoma in the breast (ACCB) is a rare subtype of breast cancer that accounts for < 0.1% of all breast-related malignancies. The majority of ACCB cases in existing literature are comprised of estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor 2 negative, abbreviated as triple-negative breast cancer. Although most triple negative breast cancers are aggressive in nature and prognosis, ACCB is reported to be more indolent with a favorable outcome. This disparity raises the question of whether the treatment approach for ACCB should follow the well-established treatment plan for other triple negative breast cancers given its atypical characteristics. Furthermore, while adenoid cystic carcinoma of the salivary glands is a well-known type of head and neck cancer with established treatment guidelines, there is limited data for recommendations regarding treatment for ACCB. We report a pathologically confirmed case of ACCB and review the existing literature regarding treatment strategy and prognosis. Case: This case is of a 69-year-old female who presented with an abnormal screening mammogram with a core needle biopsy confirming ACCB in the left lower outer quadrant. The patient was asymptomatic with no palpable masses, nipple discharge, or skin changes of the breast. Biopsy revealed adenoid cystic carcinoma grade 2, classic type, with immunochemistry confirming estrogen-receptor negative, progesterone-receptor negative, and human epidermal growth factor-receptor negative. After a thorough discussion of the options, the patient elected for breast conserving therapy and sentinel lymph node biopsy. Tumor was resected with negative margins and two out of two lymph nodes were negative for metastasis. The patient was recommended whole breast adjuvant radiation therapy given the large tumor size of 4.8cm. Chemotherapy was not recommended due to data that largely supports local targeted therapy over systemic treatment in patients without metastatic ACCB. The patient is continuing with routine follow-up evaluations. Discussion: Currently, mainstay treatment comprises of surgical resection with lumpectomy or mastectomy, with or without nodal evaluation. Radiation therapy is seen as beneficial in reducing recurrence and prolonging disease-free survival in ACCB. There is ongoing debate regarding the role of chemotherapy in ACCB patients, as triple-negative breast cancers are typically treated with a systemic chemotherapy regimen. However, since ACCB has a more favorable prognosis, the role of chemotherapy remains uncertain. With lack of data on ACCB, treatment modalities should be evaluated on a case-by-case basis. Moreover, considering the scarcity of information concerning this particular subtype of breast cancer, it is advisable to discuss these patients within a multi-disciplinary tumor board setting to ensure patients receive the maximum benefit. Citation Format: Sera Choi, Sarah Keshwani, Andrea Madrigrano. Among the < 0.1 percent of breast cancers: A case of adenoid cystic carcinoma [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-20-11.

Abstract PO3-14-08: Metaplastic Breast Cancer: Whole Genome Sequencing Analysis and Emerging Therapeutic Targets

Abstract Background: Metaplastic breast cancer (MpBC) is a rare histologic subtype of triple negative breast cancer (TNBC) with an aggressive behavior and poor outcome. Previous studies by whole-exome and targeted sequencing showed that MpBCs display a dominant mutational signature 3, associated to homologous recombination (HR) deficiency (HRD). Tumors displaying HRD are associated with response to therapies causing double strand breaks. Nonetheless, MpBCs consistently display significantly lower rates of response to neoadjuvant chemotherapy than non-metaplastic TNBCs and effective therapeutic alternatives are an unmet clinical need. Here we sought to assess the HR features of MpBCs using whole-genome sequencing (WGS), and to evaluate the expression in MpBCs of antigens that are targets of novel antibody drug conjugates (ADCs) in common forms of breast cancer. In addition, we sought to assess the efficacy of ADCs and drugs targeting the DNA damage response (DDR) using preclinical MpBC models. Materials and Methods: We subjected 25 primary MpBC to WGS. HRDetect, the ‘gold standard’ tool for assessment of HRD, was utilized. Mutational signatures were inferred using Signal. 31 MpBCs were subjected to RNA-sequencing to assess the gene expression levels ADC targets compared to non-MpBCs from The Cancer Genome Atlas (TCGA). Efficiency of ADCs and DDR drugs was evaluated using the MpBC cell models HCC1806, BT549 and Hs578T in vitroand/or using HCC1806 xenografts in athymic mice in vivo. Results: Although the majority of MpBCs (13/25) displayed a dominant SBS mutational signature 3, only a small subset of cases (3/25) were classified as HRD by HRDetect. These three bona fide HRD cases were found to harbor bi-allelic inactivation of BRCA1 (n=2) or RAD51C (n=1), and displayed various genomic features of HRD, including deletions with microhomology, enrichment in tandem duplications, rearrangement signatures 3 and 5, and high large scale state transitions (LST) and telomeric allelic imbalance (NtAI) scores. Most MpBCs (22/25), however, were not classified as HRD by HRDetect displaying an incomplete HRD phenotype, with only partial genomic features of HRD. 52% of MpBCs (13/25) displayed APOBEC mutagenesis exposure, which was present in the three bona fide HRD MpBCs. RNA-sequencing analyses revealed detectable ERBB2 and TROP2 expression in all MpBCs interrogated, although at lower levels than in non-MpBCs from TCGA. The HCC1806, BT549 and Hs578T MpBC cell models were found to be sensitive to Sacituzumab Govitecan and Trastuzumab Deruxtecan (T-DXd) in cell viability and colony formation assays, and to T-DXd in vivo. These MpBC cell models were also found to be sensitive to DDR compounds, such as ATR, WEE1 and PKMYT1 inhibitors in vitro, alone and in combination with T-DXd or Sacituzumab Govitecan. Conclusions: Most MpBCs display an incomplete HRD genomic scar, except for those cases harboring bi-allelic inactivation of HRD genes. APOBEC mutagenesis is operative in MpBCs and co-exists with HRD. MpBCs express ERBB2 and TROP2, and MpBC cell models are sensitive to T-DXd and Sacituzumab govitecan, as well as DDR compounds, targeting the incomplete HRD phenotype of MpBCs, alone and in combination. Taken together, these findings warrant further studies in patients with MpBCs testing the therapeutic efficacy of agents targeting the incomplete HRD phenotype, as well as the expression of ADC targets in these aggressive rare forms of TNBCs. Citation Format: Fresia Pareja, Andrea Gazzo, Higinio Dopeso, David Brown, Pier Selenica, Yingjie Zhu, Juan Blanco-Heredia, Laxmi Gusain, Xin Pei, Giacomo Montagna, Nour Abuhadra, Hanna Y Wen, Edi Brogi, Nadeem Riaz, Sarat Chandarlapaty, Maurizio Scaltriti, Larry Norton, Simon Powell, Jorge Reis-Filho, Britta Weigelt. Metaplastic Breast Cancer: Whole Genome Sequencing Analysis and Emerging Therapeutic Targets [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-14-08.

Abstract PS16-08: Histologic Pattern and Outcomes in High-Grade Metaplastic Breast Cancer Compared to Triple-Negative Ductal Breast Cancer Counterparts: A Single Institution Retrospective Study

Abstract Background Metaplastic breast cancer (MpBC) is a rare and aggressive subtype of breast cancer that presents with high tumor stage and a poor prognosis. MpBC tumors tend to have worse outcomes compared to other non-metaplastic triple-negative breast cancers (TNBC). Although MpBC has been described as chemotherapy resistant, chemotherapy remains a mainstay of treatment. MpBC tumors can be further characterized by their specific histologic pattern. The existing literature on outcomes of MpBC by histologic pattern is limited, with varying results regarding response rate and overall survival (OS). Identifying a pattern of MpBC that has better response to treatment could help tailor treatment recommendations. Methods A retrospective chart review was performed and identified 106 patients with early-stage, high-grade MpBC who were diagnosed at Levine Cancer Institute between January 1, 2010 and September 1, 2021. A matched control cohort (n=106) of patients diagnosed with non-metaplastic TNBC was selected based on propensity score matching on diagnosis date, age at diagnosis, race, pathologic staging, and tumor grade. Patient demographics, tumor characteristics, therapeutic interventions, residual cancer burden (RCB), and outcomes were collected. The associations between the histologic patterns of MpBC and disease characteristics were evaluated using chi-squared tests for categorical variables and Wilcoxon tests for continuous variables. We also examined the differences in RCB scores between the MpBC cohort and the non-metaplastic TNBC cohort who received neoadjuvant chemotherapy. Additionally, Kaplan-Meier and Cox proportional hazard analysis was performed to assess differences in recurrence free survival (RFS) and OS between the spindle cell/sarcomatous pattern versus all other patterns. Results For the entire group (n=212), median age at diagnosis was 58 years (range, 24-92); all patients were female; 66% White, 29% Black, and 5% unknown race. Most tumors were triple-negative (91%); 19%, 56% and 14% with Clinical Stage I, II, and III disease, respectively. A total of 63% of patients underwent radiation treatment and 76% received chemotherapy (43% neoadjuvant and 57% adjuvant). Recurrence after treatment occurred in 16% of all patients. In the MpBC cohort (n=106), the histologic patterns included spindle cell/sarcomatous (34%), squamous (17%), heterologous mesenchymal (31%), mixed (17%), and other (1%). Of those with MpBC who received neoadjuvant chemotherapy (n=32), RCB among the different histologic patterns was assessed. When comparing spindle cell/sarcomatous versus the other histologic patterns combined, there was no significant difference in RCB (p = 0.81), although more RCB III scores were recorded in the spindle cell/sarcomatous pattern compared to the other MpBC patterns (40% versus 30%). When assessing RFS and OS by histologic pattern in the entire MpBC cohort, spindle cell/sarcomatous tumors had inferior RFS (p = 0.0194) and OS (p = 0.0039) compared to the other MpBC patterns combined. When comparing RCB values between MpBC and non-metaplastic TNBC, there were numerically more RCB-III classes in the MpBC cohort as compared to the non-metaplastic TNBC. Conclusion MpBC is an aggressive and difficult breast malignancy to treat. Based on our single institution review, no correlation between RCB and the histologic pattern of MpBC was found, however, RFS and OS were worse among the spindle cell/sarcomatous pattern. Furthermore, the MpBC cohort had numerically higher RCB-III scores than the TNBC control cohort, which is in line with historical data. Citation Format: Ashley Matusz-Fisher, Annabel Chen, Erin Donahue, Courtney Schepel, Michelle Wallander, Chad Livasy, Richard White, Antoinette Tan, Lejla Hadzikadic-Gusic. Histologic Pattern and Outcomes in High-Grade Metaplastic Breast Cancer Compared to Triple-Negative Ductal Breast Cancer Counterparts: A Single Institution Retrospective Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS16-08.

Cytomorphological features of sebaceous carcinoma of the breast.

Sebaceous carcinoma of the breast is an extremely rare histological subtype of breast cancer, with fewer than 30 cases reported to date. Because of its extremely rare histological presentation, there are few case reports that highlight its cytological findings. In this case report, the cytomorphological features of a sebaceous carcinoma of the breast are described in detail. Cytomorphological analysis revealed atypical cells presenting predominantly as loose clusters. No tubular or papillary structures were evident in the clusters and no mucin production was observed. The diagnosis of sebaceous carcinoma of the breast requires prominent sebaceous differentiation of cells. In Papanicolaou-stained smears, the differentiated tumor cells were found within the yellowish clusters. When these yellowish clusters were observed at high magnification and shifted out of focus, the sebaceous differentiation of tumor cells could be recognized. This finding is an advantage of observing Papanicolaou-stained specimens. Like previous reports, some individual cells showing sebaceous differentiation were also observed. In cases where many yellowish clusters appear, close observation of the interior of the clusters can confirm the presence of sebaceous differentiation of tumor cells and serve as a diagnostic clue for the cytological diagnosis of sebaceous carcinoma of the breast.

Rare Presentation of Papillary Carcinoma Within a Sentinel Lymph Node in a Patient With Ductal Carcinoma in Situ of the Breast: A Challenging but Useful Case Report Discussion Regarding Displacement or True Metastasis?

Papillary carcinoma of the breast is a rare histologic subtype of invasive breast cancer. In contrast, ductal carcinoma in situ (DCIS) is a noninvasive, nonobligate precursor to invasive mammary carcinoma, confined within the terminal duct lobular unit of the breast and surrounded by an intact myoepithelial cell layer at the stromal/epithelial interface. We present an unusual case in which a patient with only DCIS of the breast exhibited papillary carcinoma within a sentinel lymph node, leading to questions about the origin of the lymph node lesion-whether it represents a true metastasis or iatrogenic displacement during diagnostic procedures. This case underscores the diagnostic challenges and clinical implications associated with such rare presentations.

A prognostic nomogram based on least absolute shrinkage and selection operator Cox regression in patients with pulmonary large-cell neuroendocrine carcinoma.

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare subtype of breast cancer with a poor prognosis. Despite its rarity, it is important to gain a better understanding of the epidemiological, clinical, and prognostic features of pulmonary LCNEC. The purpose of this study was to design, construct, and validate a new nomogram for predicting overall survival (OS) in patients with pulmonary LCNEC. In total, the data of 1,864 LCNEC patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database, which is maintained by the National Cancer Institute in the United States and serves as a comprehensive source of cancer-related information. Of these patients, 556 served as the validation group and 1,308 served as the training cohort. We constructed a new nomogram with the training cohort that included the independent factors for OS as identified by least absolute shrinkage and selection operator Cox regression. Five independent factors were ultimately selected by the stepwise regression. Every factor of the Cox regression was included in the nomogram. Analyses of the calibration curve, decision curve, area under the curve, and concordance index (C-index) values were performed to assess the effectiveness and discriminative ability of the nomogram. Five optimal predictive factors for OS were selected and merged to construct a 3- and 5-year OS nomogram. The nomogram had C-index values of 0.716 and 0.708 in the training cohort and validation cohort, respectively. The actual OS rates and the calibration curves showing the predictions of the nomogram were in good agreement. The prognostic nomogram may be very helpful in estimating the OS of patients with pulmonary LCNEC.

Identification of barriers at the primary care provider level to improve inflammatory breast cancer diagnosis and management

The purpose of this study, based in the United States, was to evaluate knowledge gaps and barriers related to diagnosis and care of inflammatory breast cancer (IBC), a rare but lethal breast cancer subtype, amongst Primary Care Providers (PCP) as they are often the first point of contact when patients notice initial symptoms. PCP participants in the Duke University Health System, federally qualified health center, corporate employee health and community practices, nearby academic medical center, Duke physician assistant and advanced practice nurse leadership program alumni were first selected in a convenience sample and for semi-structured interviews (n = 11). Based on these data, an online survey tool was developed and disseminated (n = 78) to assess salient measures of IBC diagnosis, health disparity factors, referral and care coordination practices, COVID-19 impact, and continuing medical education (CME). PCP reported access to care and knowledge gaps in symptom recognition (mean = 3.3, range 1–7) as major barriers. Only 31 % reported ever suspecting IBC in a patient. PCP (n = 49) responded being challenged with referral delays in diagnostic imaging. Additionally, since the COVID-19 pandemic started, 63 % reported breast cancer referral delays, and 33 % reported diagnosing less breast cancer. PCP stated interest in CME in their practice for improved diagnosis and patient care, which included online (53 %), lunch time or other in-service training (33 %), patient and provider-facing websites (32 %). Challenges communicating rare cancer information, gaps in confidence in diagnosing IBC, and timely follow-up with patients and specialists underscores the need for developing PCP educational modules to improve guideline-concordant care.

Secretory breast carcinoma: clinicopathological features and prognosis of 52 patients.

Secretory breast carcinoma is a rare histological subtype of invasive breast cancer and considered with an indolent clinical behavior. This study was conducted to analyze the clinicopathological features of patients with secretory breast carcinoma (SBC), explore the outcome, and compare the prognostic difference with invasive ductal breast carcinoma (IDC). METHODSAND MATERIALS: Patients with SBC diagnosed between 2006 and 2017 from Fudan University Shanghai Cancer Center were included in the study, excluding patients with previous malignant tumor history and incomplete clinical data or follow-up records. Peculiar clinicopathological and immunohistochemical features of the cases were fully described. Clinical data of 4979 cases of IDC were also evaluated during this period. After propensity score matching, prognostic analysis of SBCs and IDCs was calculated by Kaplan-Meier method and landmark analysis method. The data of 52 patients diagnosed with SBC were identified from the pathological files. Among them, 47 patients were women, and 5 were men. The median age of the 52 SBCs was 46years (mean, 48.1years; range, 10-80years). The tumor sizes ranged from 0.3 to 6.8cm, with a mean of 3.5cm. Eight patients (15.4%) had positive axillary lymph node involvement. The molecular classification was mostly triple-negative breast cancer (65.4%). Fluorescence in situ hybridization confirmed the presence of ETV6::NTRK3 rearrangement in 16 of 18 cases (88.9%). Furthermore, Kaplan-Meier survival analysis and landmark analysis demonstrated that there were no statistically significant differences in DFS and OS between SBC and IDC patients. Although SBCs are generally associated with a favorable prognosis, our work exhibited that the clinicopathological features of SBC were partly different from former understandings, indicating that therapeutic procedure should be prudent. Further studies are necessary to fully identify the clinical behavior and predictive markers to improvediagnosis and management in this unique subtype of breast cancer.

Construction and validation of a nomogram for predicting the prognosis of patients with lymph node-positive invasive micropapillary carcinoma of the breast: based on SEER database and external validation cohort

BackgroundInvasive micropapillary carcinoma (IMPC) of the breast is a rare subtype of breast cancer with high incidence of aggressive clinical behavior, lymph node metastasis (LNM) and poor prognosis. In the present study, using the Surveillance, Epidemiology, and End Results (SEER) database, we analyzed the clinicopathological characteristics and prognostic factors of IMPC with LNM, and constructed a prognostic nomogram.MethodsWe retrospectively analyzed data for 487 breast IMPC patients with LNM in the SEER database from January 2010 to December 2015, and randomly divided these patients into a training cohort (70%) and an internal validation cohort (30%) for the construction and internal validation of the nomogram, respectively. In addition, 248 patients diagnosed with IMPC and LNM at the Fourth Hospital of Hebei Medical University from January 2010 to December 2019 were collected as an external validation cohort. Lasso regression, along with Cox regression, was used to screen risk factors. Further more, the discrimination, calibration, and clinical utility of the nomogram were assessed based on the consistency index (C-index), time-dependent receiver operating characteristic (ROC), calibration curve, and decision curve analysis (DCA).ResultsIn summary, we identified six variables including molecular subtype of breast cancer, first malignant primary indicator, tumor grade, AJCC stage, radiotherapy and chemotherapy were independent prognostic factors in predicting the prognosis of IMPC patients with LNM (P < 0.05). Based on these factors, a nomogram was constructed for predicting 3- and 5-year overall survival (OS) of patients. The nomogram achieved a C-index of 0.789 (95%CI: 0.759-0.819) in the training cohort, 0.775 (95%CI: 0.731-0.819) in the internal validation cohort, and 0.788 (95%CI: 0.756-0.820) in the external validation cohort. According to the calculated patient risk score, the patients were divided into a high-risk group and a low-risk group, which showed a significant difference in the survival prognosis of the two groups (P<0.0001). The time-dependent ROC curves, calibration curves and DCA curves proved the superiority of the nomogram.ConclusionsWe have successfully constructed a nomogram that could predict 3- and 5-year OS of IMPC patients with LNM and may assist clinicians in decision-making and personalized treatment planning.

Lobular-Like Features and Outcomes of Mixed Invasive Ductolobular Breast Cancer (MIDLC): Insights from 54,403 Stage I-III MIDLC Patients.

Mixed invasive ductolobular breast cancer (MIDLC) is a rare histological subtype of breast cancer (BC), with components of both invasive ductal cancer (IDC) and invasive lobular cancer (ILC). Its clinicopathological features and outcomes have not been well characterized. The National Cancer Database 2010-2017 was reviewed to identify women with stage I-III BCs. Univariate analysis was performed using Chi-square or Wilcoxon rank-sum tests and multivariable analysis with logistic regression to predict surgical decisions. Survival was assessed using multivariable Cox proportional hazards regression analysis. We identified 955,828 women with stage I-III BCs (5.7% MIDLC, 10.3% ILC, and 84.0% IDC). MIDLC was more like ILC than IDC in terms of multicentricity (14.2% MIDLC, 13.0% ILC, 10.0% IDC), hormone receptor positivity (96.6% MIDLC, 98.2% ILC, 81.2% IDC), and use of neoadjuvant chemotherapy (NAC; 5.8% MIDLC, 5.2% ILC, 10.8% IDC). 744,607 women underwent upfront surgery. The mastectomy rates were 42.3% for MIDLC, 46.5% for ILC, and 33.3% for IDC (all p<0.001). With 5.5 years of median follow-up, the adjusted overall survival in the upfront surgery hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) biological subgroup was better in MIDLC (hazard ratio 0.88, p<0.001) and ILC (hazard ratio 0.91, p<0.001) than in IDC. Like ILC, MIDLC also had a lower pathological complete response to NAC than IDC (12.3% MIDLC, 7.3% ILC, 28.6% IDC). MIDLC displays a mixed pattern of characteristics favoring features of ILC compared with IDC, with favorable 5-year overall survival compared with IDC within the HR+/HER2- subtype who underwent upfront surgery.

Spindle Cell Carcinoma of the Breast in a Patient with Previous History of Rectal Cancer: A Case Report

Abstract Background Spindle cell carcinoma of the breast is a very rare subtype of metaplastic breast cancer with aggressive behaviour in comparison with invasive ductal carcinoma, which is the most common histological type of breast cancer. It has a poor prognosis and a controversial response to systemic therapy. Aim of this study The aim of this study is to shed light on this uncommon but aggressive type of breast cancer. Case Presentation In this case report, we present a 56-year-old woman with spindle cell carcinoma of the breast with a previous history of treated rectal cancer. She presented with a left breast mass. Ultrasound-guided fine needle aspiration gave results positive for malignancy. A left mastectomy with axillary clearance was done, and the histopathology was spindle cell carcinoma of the breast. The patient refused chemotherapy until five months post-operation when she presented with local recurrence of two small masses at the site of mastectomy. New imaging revealed bilateral pulmonary metastasis. She started on single agent Adriamycin and received a total of six cycles. A CT scan of the chest and abdomen with contrast revealed disease progression. Imaging of the brain showed brain metastasis. The patient refused any kind of further chemotherapy or radiotherapy treatment until she passed away one month later from aspiration pneumonia and its complications. Conclusion Metaplastic breast cancer is an aggressive subtype of breast cancer with rapid progression, a high tendency for distant metastases, a poor response to treatment, and a short survival time.

Intratumoral 99mTc-DPD Uptake on Bone Scintigraphy in a Patient With Invasive Micropapillary Breast Carcinoma: A Pathologic Review.

Invasive micropapillary carcinoma (IMPC) is a rare and aggressive subtype of breast cancer with a poorer prognosis due to high local recurrence and lymphovascular invasion. Interestingly, IMPC often does not show suspicious patterns of calcifications related to malignancy on mammography. Therefore, the lack of suspicious calcifications makes it difficult to detect breast cancer on mammography. With only nonspecific calcifications on mammography, we observed an unusual intratumoral 99mTc-DPD uptake on whole-body bone scintigraphy in an IMPC breast cancer patient during the initial staging workup, and its characteristics were compared with mammographic findings and the postoperative pathologic features.

Bioinformatics analysis of human kallikrein 5 (KLK5) expression in metaplastic triple‐negative breast cancer

AbstractBackgroundMetaplastic breast carcinoma (MBC) is a rare breast cancer subtype; most cases are triple‐negative breast cancers (TNBCs) and are poorly responsive to conventional systemic therapy. Few potential diagnostic and prognostic markers for distinguishing between metaplastic TNBC and nonmetaplastic TNBC have been discovered. We performed bioinformatic analysis to explore the underlying mechanism by which metaplastic TNBC differs from nonmetaplastic TNBC and provides potential pathogenic genes of metaplastic TNBC.MethodsDifferentially expressed genes (DEGs) in metaplastic tumors and nonmetaplastic tumors from TNBC patients were screened using GSE165407. The GSE76275 data set and The Cancer Genome Atlas (TCGA) database were used to screen DEGs in TNBC and non‐TNBC. Metascape and DAVID were used for the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Gene Ontology (GO) analysis of DEGs. Online databases, including UALCAN, GEPIA, HPA, Breast Cancer Gene‐Expression Miner, and quantitative PCR and western blot, were used to examine KLK5 messenger RNA and protein expression in breast cancer. Analysis of KLK5‑associated genes was performed with TCGA data, and the LinkedOmics database was used to detect the genes co‐expressed with KLK5. STRING (Search Tool for the Retrieval of Interacting Genes) and Cytoscape were used to screen for hub genes. Kaplan‑Meier plotter was used for survival analysis.ResultsKLK5 was identified among the DEGs in nonmetaplastic TNBC and metaplastic TNBC. The KLK5 gene was overexpressed in nonmetaplastic TNBC but downregulated in metaplastic TNBC. KEGG and GO analyses revealed that epithelial‐to‐mesenchymal transition was a pathogenic mechanism in metaplastic TNBC and an important pathway by which KLK5 and its associated genes DSG1 and DSG3 influence metaplastic TNBC progression. Prognosis analysis showed that only low expression of KLK5 in metaplastic TNBC had clinical significance.ConclusionOur research indicated that KLK5 may be a pivotal molecule with a key role in the mechanism of tumorigenesis in metaplastic TNBC.

A case report and literature review on a rare subtype of triple-negative breast cancer in children

BackgroundTriple-negative breast cancer (TNBC) is a type of breast tumor with a poor prognosis because it lacks or expresses low levels of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2). TNBC is more common in middle-aged and older women, and cases of TNBC in children are rarely reported. This is the only case of childhood SBC in our hospital in more than 70 years, and the disease is extremely rare internationally. We analyzed and studied the disease and TNBC from both clinical and pathological aspects and found that SBC is very different from TNBC.Case presentationWe report a case of secretory breast cancer (SBC), a subtype of TNBC, in an 8-year-old girl from our institution. The child presented with a single mass in the left breast only, with no skin rupture and no enlargement of the surrounding lymph nodes. The child underwent two surgeries and was followed up for one year with a good prognosis.ConclusionsSBC is highly prevalent among the multiple pathological types of pediatric breast cancer. Almost all pediatric SBC patients are characterized by the ETV6-NTRK3 fusion gene, which has a good prognosis and a 10-year survival rate of more than 90% when compared with other TNBC subtypes. According to the patient, we performed local mass resection and a postoperative pathological diagnosis of SBC (a subtype of BL-TNBC). The TNBC case had a good prognosis and differed from basal TNBC in several aspects, including clinical presentation, treatment, and prognosis. It is necessary to exclude SBC from BL-type TNBC, enhance understanding of the disease, and individualize the treatment plan, so as to avoid medical errors.

Epidemiological and survival outcomes of neuroendocrine carcinoma of the breast: a SEER data analysis.

Neuroendocrine carcinoma of the breast (NECB) is a rare subtype of breast cancer, comprising only 0.1% to 5% of all breast cancer cases. Despite its rarity, it is important to gain a better understanding of the epidemiological, clinical, and prognostic features of NECB. The purpose of the study was to obtain population-based evaluations of the epidemiological and survival outcomes of NECB. The data of patients with neuroendocrine carcinoma diagnosed and enrolled between 2000 and 2017 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Descriptive statistical analyses were used to assess the distribution and tumor-related characteristics of these patients. Kaplan-Meier curves and univariate and multivariate Cox proportional risk models were used to analyze variables that might be associated with prognosis. This study included 7,856 patients with neuroendocrine carcinoma. The median age of the patients was 64 years, and most of them were female, White, and diagnosed at ≥60 years old. The most common pathological type was neoplasm. Survival analysis indicated that there were significant differences in age, marital status, registration location, American Joint Committee on Cancer (AJCC) stage, breast subtype, surgery of primary tumor, and no cancer cause surgery patients with NECB. The results also indicated that treatment with surgery, including surgery of primary tumor, surgery combined with radiation, and no cancer cause surgery, were all effective in improving the prognosis compared with not providing surgical treatment. In conclusion, NECB is a very rare lesion for which age, marital status, registration location, and surgery, AJCC stage, breast subtype were found to be independent prognostic factors.

Comparison of clinicopathologic characteristics of Invasive Papillary Carcinoma with Invasive Ductal Carcinoma and their survival outcome

Background: Invasive Papillary Carcinoma (IPC) of the breast is a rare breast cancer subtype. This study aimed to evaluate the clinicopathologic characteristics of IPC of the breast, its differences from Invasive Ductal Carcinoma (IDC), and their survival outcomes.Materials and Methods: The medical records of 6599 patients were retrospectively reviewed at the Breast Disease Research Center from December 1993 to December 2021. The patients were divided into two groups: IPC and IDC. The tumor size, lymph node metastasis, pathologic stage, nuclear and histological grade, hormonal receptor status, and survival were reviewed and compared between the IPC and IDC groups.Results: Of the 6599 patients, 27 had IPC, and 6572 had IDC. The mean age of patients with IPC and IDC was 58.5 and 49 years, respectively (P=0.02). Patients with IPC were more likely to have a positive node status and had a significantly higher incidence of lymphovascular invasion (14.9% for IPCs and 53.3% for IDCs, P&lt;0.001). ER status was positive in 66.6% of IPCs and 78.1% of IDCs (P=0.23). Additionally, 62.5% of patients with IPC and 94.9% of those with IDC received adjuvant chemotherapy (P&lt;0.001). Disease-free survival (DFS) and overall survival (OS) were better in IPC patients for stage I (5-year DFS: 69% vs. 81%, P=0.008; 5-year OS: 75% vs. 85%, P=0.001).Conclusion: IPC is a rare tumor type that presents unique clinicopathological characteristics and is associated with a higher rate of breast-conserving surgery and a favorable prognosis than IDC

Development and validation of competitive risk model for older women with metaplastic breast cancer

BackgroundMetaplastic breast cancer (MpBC) is a rare histological subtype of breast cancer. This study aims to establish a competitive risk model for older women with MpBC to predict patients’ survival accurately.MethodsData on patients diagnosed with MpBC from 2010 to 2019 are from the Surveillance, Epidemiology and End Results (SEER) program in the United States. All patients were randomly assigned to the training set and validation set. The proportional sub-distribution risk model was used in the training set to analyze the risk factors affecting patient death. Based on the risk factors for cancer-specific mortality (CSM) in patients, we constructed a competitive risk model to predict patients’ 1-, 3-, and 5-year cancer-specific survival. Then we used the concordance index (C-index), the calibration curve and the area under the receiver operating characteristic curve (AUC) to validate the discrimination and accuracy of the model.ResultsOne thousand, four hundred twelve older women with MpBC were included in this study. Age, T stage, N stage, M stage, tumor size, surgery and radiotherapy were risk factors for CSM. We established a competitive risk model to predict 1-, 3-, and 5-year cancer-specific survival in older women with MpBC. The C-index of the model was 0.792 in the training set and 0.744 in the validation set. The calibration curves in the training and validation sets showed that the model’s predicted values were almost consistent with the actual observed values. The AUC results show that the prediction model has good accuracy.ConclusionWe developed a competitive risk model based on these risk factors to predict cancer-specific survival in older women with MpBC. The validation results of the model show that it is a very effective and reliable prediction tool. This predictive tool allows doctors and patients to make individualized clinical decisions.

Genomic characteristics of triple negative apocrine carcinoma: a comparison to triple negative breast cancer.

Apocrine carcinoma is a rare breast cancer subtype. As such, the genomic characteristics of apocrine carcinoma with triple negative immunohistochemical results (TNAC), which has been treated as triple negative breast cancer (TNBC), have not been revealed. In this study, we evaluated the genomic characteristics of TNAC compared to TNBC with low Ki-67 (LK-TNBC). In the genetic analysis of 73 TNACs and 32 LK-TNBCs, the most frequently mutated driver gene in TNAC was TP53 (16/56, 28.6%), followed by PIK3CA (9/56, 16.1%), ZNF717 (8/56, 14.3%), and PIK3R1 (6/56, 10.71%). Mutational signature analysis showed enrichment of defective DNA mismatch repair (MMR)-related signatures (SBS6 and SBS21) and the SBS5 signature in TNAC, whereas an APOBEC activity-associated mutational signature (SBS13) was more prominent in LK-TNBC (Student's t test, p < 0.05). In intrinsic subtyping, 38.4% of TNACs were classified as luminal A, 27.4% as luminal B, 26.0% as HER2-enriched (HER2-E), 2.7% as basal, and 5.5% as normal-like. The basal subtype was the most dominant subtype (43.8%) in LK-TNBC (p < 0.001), followed by luminal B (21.9%), HER2-E (21.9%), and luminal A (12.5%). In the survival analysis, TNAC had a five-year disease-free survival (DFS) rate of 92.2% compared to 59.1% for LK-TNBC (P = 0.001) and a five-year overall survival (OS) rate of 95.3% compared to 74.6% for LK-TNBC (P = 0.0099). TNAC has different genetic characteristics and better survival outcomes than LK-TNBC. In particular, normal-like and luminal A subtypes in TNAC have much better DFS and OS than other intrinsic subtypes. Our findings are expected to impact medical practice for patients diagnosed with TNAC.