Germline BRCA2 Pathogenic Variant in Primary Breast Cancer of a Down Syndrome Individual.

BACKGROUND Down syndrome (DS) is the most common genetic disorder, and individuals with DS are known to have a low risk for solid tumors, including breast cancer. In contrast, Breast Cancer Susceptibility Gene (BRCA) pathogenic variant can cause breast cancer. We report a case of primary breast cancer harboring a BRCA2 pathogenic variant in a 35-year-old woman with DS. CASE REPORT A 35-year-old woman with DS presented with a palpable 2-cm mass in the upper-inner quadrant of the left breast. A biopsy confirmed an invasive ductal carcinoma of the breast. Her clinical diagnosis was cT2, N0, M0, cStageIIA. A left modified radical mastectomy with axillary node dissection was performed. Her final pathological diagnosis was invasive ductal carcinoma (T2, pN1, M0, stageIIB), positive estrogen receptors, negative progesterone receptors, negative human epidermal receptor-2 status. She was started on adjuvant hormonal therapy. Unfortunately, 23 months after the operation, multiple metastases were detected. Testing for a BRCA pathogenic variant was performed, and a BRCA2 pathogenic variant was detected. Olaparib was orally administered, and the levels of tumor markers rapidly declined; however, the levels of the tumor markers started to increase again 5 months after the initiation of olaparib. Subsequently, she developed bilateral carcinomatous lymphangiomatosis and died 59 months after the operation. CONCLUSIONS This report highlights a rare case of primary breast cancer harboring a germline BRCA2 pathogenic variant in an individual with DS. Our study highlights the importance of genetic testing as part of breast cancer management in these patients.

Salivary Ductal Carcinoma: A Case Report.

ABSTRACT: Salivary ductal carcinoma is an extremely rare tumor located in the parotid gland. This case details a salivary ductal carcinoma within the parotid gland of a 59-year-old man and its management.

Factors influencing suboptimal pathologic margins and re-excision following breast conserving surgery for ductal carcinoma in-situ.

INTRODUCTION: Re-excisions following breast conserving surgery (BCS) are common, occurring more frequently in ductal carcinoma in-situ (DCIS) than its' malignant counterpart. Although one quarter of patients with breast cancer will have DCIS, there is limited information available regarding factors predisposing to inadequate pathologic margins, and the need for re-excision. METHODS: Retrospective review of patients treated for DCIS between the years 2010-2016 was conducted. Patients with DCIS undergoing BCS were identified and evaluated for demographic and pathologic factors associated with suboptimal pathologic margins and re-excision. Multivariate analysis with Wald Chi-Square testing was performed. RESULTS: 241 patients underwent BCS with suboptimal margins (SOM) in 51.7% (123/238), with 27.8% undergoing re-excision (67/241). Tumor size was the most influential variable, positively associated with SOM (OR = 10.25, CI: 5.50-19.13) and re-excision (OR = 6.36, CI: 3.92-10.31). Patient age was inversely associated with SOM (OR = 0.58, CI: 0.39-0.85) and subsequent re-excisions (OR = 0.56, CI: 0.36-0.86). Low tumour grade was associated with re-excision (OR = 1.31, CI: 0.63-2.71), while ER negative disease was associated with SOM (OR = 2.24, CI: 1.21-4.14). DISCUSSION: Inadequate pathologic margins following BCS, and subsequent re-excision rates are common in patients with DCIS, and consistent with the literature. Tumour size is the dominant factor driving this occurrence, with patient age and tumour grade also impacting outcomes.

The Role of Cryoablation in Breast Cancer Beyond the Oncologic Control: COST and Breast-Q Patient-Reported Outcomes.

BACKGROUND: Cryoablation has been established as a minimally invasive alternative to resection of early-stage breast cancer; however, there are no data on the cost and impact on patients' financial, psychosocial, sexual, physical, and cosmetic outcomes utilizing this approach. This study compares cost-effectiveness and patient-reported quality-of-life factors in cryoablation versus resection. METHODS: Women with early-stage, low-risk infiltrating ductal carcinomas ≤ 1.5 cm underwent cryoablation or resection. Adjuvant therapy was provided according to tumor board recommendations. Direct and indirect costs were tracked for both groups. Financial toxicity and well-being outcome were measured by administering the Comprehensive Score of Financial Toxicity (COST) and BREAST-Q surveys, respectively, at 6-month follow-up. RESULTS: Of the 34 eligible patients, 14 (41.1%) consented for cryoablation and 20 (58.8%) underwent resection. The median (centile) (range) follow-up was 35.0 (21.3) (15-50) months for cryoablation vs. 25 (20.8) (17-50) months for resection [p = 0.6479]. Mean (standard deviation) cost of care for cryoablation versus resection was $2221.70 (615.70) versus $16,896.50 (1332.40) [p < 0.0001], and median financial well-being scores for the cryoablation versus resection groups were 38.0 (34.5, 40.0) versus 10 (5.3, 14.0) [p < 0.0001]. Poor financial well-being was directly correlated with the cost of care [p < 0.0001]. Median psychosocial well-being scores were similar across both groups, however the cryoablation group had higher scores for physical [100 (100, 100) vs. 89 (79, 100); p = 0.0141], sexual [100 (91, 100) vs. 91 (87.5, 91); p = 0.0079], and cosmetic [100 (100, 100) vs. 88 (88, 100); p = 0.0171] outcomes. CONCLUSION: Cryoablation offers a cost-effective and quality-of-life advantage compared with resection for early-stage, low-risk breast cancer.

[Invasive Ductal Carcinoma within a Borderline Malignancy Phyllodes Tumor-A Case Report].

Phyllodes tumors are uncommon breast neoplasms that constitute 1-2% of breast malignancies. Invasive ductal carcinoma in the epithelial component of phyllodes tumor is very rare. When carcinoma is detected within the specimen, the management of treatment changes completely. We report a rare case of invasive ductal carcinoma arising in a giant borderline malignancy phyllodes tumor in a 51-year-old female patient. A painful 20 cm mass was found in her right breast, and a needle biopsy revealed fibroadenoma or benign phyllodes tumor, and a total mastectomy was performed. Pathological results showed that a borderline malignant phyllodes tumor coexisted with invasive ductal carcinoma. We explained that axillary surgery was necessary because invasive cancer was diagnosed after surgery, but the patient requested follow-up using images. Endocrine therapy was performed as postoperative adjuvant therapy, and the follow-up is underway without recurrence.

Asynchronous bilateral male breast cancer. A rare case report.

We describe a rare case of asynchronous bilateral carcinoma of the mammary glands in a 66-year-old man. The patient was admitted to the Department of Dermatology and Venereology due to exacerbation of chronic eczema. During the examination, a 3×2-cm tumor with retraction of the mammilla was found in the right mammary gland. Mastectomy and regional lymphatic dissection were performed. Histological examination showed invasive ductal carcinoma, ER (+) 70%, PR (-), HER2 (-). Treatment included chemotherapy, radiotherapy, and hormone therapy. Three years later, the patient reported a lump in the left breast. The presence of a tumor formation was confirmed by mammography and ultrasound examination. A radical mastectomy with regional lymphatic dissection was performed. Histological examination showed invasive ductal carcinoma of the mammary gland, ER (3+) 80%, PP (2+) 60%, HER2 (+++), and Ki67 (+) 80%. Treatment with chemotherapy and radiation therapy was carried out. Five years after diagnosis of the second carcinoma, the patient is in a good general condition. Regardless of its rarity, the described case should draw doctors' attention to this pathology. Assessment of risk factors and periodic breast examination in men would allow early diagnosis, timely treatment, and better prognosis of the disease.

Gynecomastia and Malignancy: A Case of Male Invasive Ductal Breast Carcinoma Treated with Neoadjuvant Chemotherapy.

BACKGROUND Male breast cancer represents a rare malignancy with identifiable risk factors, including genetics, radiation exposure, liver dysfunction, and concomitant diagnosis of Klinefelter syndrome. Gynecomastia can commonly present in these patients, and despite increased estrogen levels in adipose breast tissue, gynecomastia has not been proven to be a significant risk factor for carcinoma development. Male patients with new-onset breast masses are recommended to undergo diagnostic mammograms and breast ultrasound for further evaluation. Those diagnosed with breast cancer most commonly have invasive ductal carcinoma of the breast, and over half of these patients are found to have estrogen and progesterone receptor (ER/PR) positivity. CASE REPORT In this case report, we present a Black man with gynecomastia and an areolar lesion for a 6-month duration following a traumatic event. He was initially referred to the surgical team for further evaluation, and subsequent imaging and biopsy data revealed ER/PR-positive invasive ductal carcinoma. Multidisciplinary discussions were held, and the patient was arranged to begin neoadjuvant treatment with doxorubicin hydrochloride and cyclophosphamide, followed by treatment with paclitaxel (AC-T) chemotherapy, followed by bilateral mastectomy and adjuvant hormonal therapy. CONCLUSIONS The treatment of male breast cancer has remained relatively like that of female breast cancer, which may be due to the limited data in the treatment of male breast cancer. Thus far, studies involving neoadjuvant chemotherapy of female patients have demonstrated promising responses to expand surgical options for patients and possibly decrease the rates of recurrence. Additional studies are warranted to discern optimal therapy for the male patient population.

Invasive and Non-invasive Ductal Carcinoma within Malignant Phyllodes Tumour with Axillary Lymph Node Metastases.

Phyllodes tumours are uncommon breast neoplasms constituting 1-2% of breast malignancies. Metastasis is usually haematogenous, and axillary lymph node dissection is not routinely performed. A phyllodes tumour with concomitant invasive ductal carcinoma (IDC) is even rarer. When IDCor ductal carcinoma in-situ (DCIS) is detected, the management of the condition changes completely. We report a case of a 22-year female presenting with a mass in the right breast and palpable axillary lymph nodes. The pathological examination demonstrated a malignant phyllodes tumour with concomitant IDC and DCIS. The patient elected to have modified radical mastectomy, and the pathological examination showed metastasis in the axillary lymph nodes. The patient was administered appropriate therapy. At the last visit, she did not have the clinical signs of disease. This is the first youngest case of axillary lymph node metastases with both DCIS and IDC on pathological examination in malignant phyllodes tumour. Key Words: Malignant phyllodes, Invasive ductal carcinoma, Ductal carcinoma in-situ, Lymph node metastasis.

Secretory Carcinoma of the Breast Mimicking Invasive Ductal Carcinoma: A Case Report.

BACKGROUND Secretory breast carcinoma (SBC), an extremely rare malignancy, is related to a chromosomal translocation which leads to an ETV6-NTRK3 fusion mutation. SBC is characterized by eosinophilic secretions and is usually triple-negative, with a small number of patients demonstrating ER-positivity of the tumors. Diagnosis can be challenging and requires genomic testing for confirmation. CASE REPORT A 40-year-old woman presented with a breast mass found on mammography. She underwent an ultrasound-guided biopsy of the tumor. Initial pathology evaluation revealed features consistent with invasive ductal carcinoma. The immunochemistry report described an ER-positive, PR-negative, and HER2-negative tumor. The specimen was sent for oncotype scoring, which was not performed due to the specimen not meeting the criteria for invasive ductal carcinoma and displaying pathological features of SBC. A fluorescent in situ hybridization (FISH) study revealed ETV6 translocation, consistent with the diagnosis of SBC. The patient underwent lumpectomy followed by adjuvant radiotherapy and endocrine therapy. She remains in complete remission 3 years after treatment. CONCLUSIONS Accurately diagnosing SBC is of extreme importance as it has an indolent clinical course, but has a favorable prognosis if detected early. Due to nonspecific imaging findings, pathology evaluation with immunohistochemical staining followed by genomic testing is required. Our case highlights the challenges associated with SBC diagnosis requiring genomic testing due to equivocal pathological findings, along with increasing incidence of SBT in adults. There are no established guidelines for SBC management. The mainstay of treatment is partial or total mastectomy. Data on the benefits of adjuvant endocrine therapy, chemotherapy, and radiotherapy are inconclusive.

Radiofrequency spectroscopy with intraoperative pathological assessment for breast carcinoma: synergistic or redundant?

BACKGROUND: Published MarginProbe (Dune Medical Devices Ltd., Israel) data reports ≥50% reduction in positive lumpectomy margins. We sought to determine whether adjunctive use of MarginProbe would provide value over intraoperative pathologic assessment alone. METHODS: This is a retrospective chart review of 86 consecutive lumpectomies with MarginProbe from December 2018 to November 2019. Margins were considered positive using 'no ink on tumor' guideline for invasive cancer, and 2 mm or greater for ductal carcinoma in-situ. Significance was measured using Fisher's exact test. RESULTS: Seventy-six patients yielded 86 lumpectomies for inclusion. Mean age was 69.8 and mean tumor size was 1.09 cm. Sixty-eight invasive cancers were assessed using adjunct MarginProbe and gross assessment, while 18 ductal carcinoma in-situ cases utilized MarginProbe only. Among all cases, gross assessment alone reduced positive margins(29.2% relative reduction, p = 0.28). Utilizing both modalities, positive margins decreased from 27.9% to 9.3% (66.7% relative reduction, p < 0.01) representing a 46.9% relative reduction versus gross assessment alone. After gross assessment and MarginProbe evaluation, additional excised volume averaged 2.9 cc. CONCLUSIONS: Synergistic use of MarginProbe and gross assessment reduces positive margins during breast conserving surgery. Surgeons can weigh its cost against it benefit with the succinct analysis we provide.

Squamoid Eccrine Ductal Carcinoma: Treatment and Outcomes.

BACKGROUND: Squamoid eccrine ductal carcinoma (SEDC) represents a subtype of eccrine carcinomas that are diagnostically challenging for both clinicians and dermatopathologists. OBJECTIVE: To provide an updated review of SEDC and examine patient outcomes with different treatment modalities. METHODS: A review of Ovid MEDLINE was performed to review the English language medical literature of SEDC. RESULTS: A comprehensive review of clinical presentation, histologic findings, rates of lymphovascular and metastatic disease, treatment modalities and recurrence rates are reviewed. LIMITATIONS: There is a limitation on available data because of the rare incidence. CONCLUSIONS: SEDC is a rare adnexal neoplasm with a relatively high rate of local recurrence, lymphovascular invasion, perineural invasion, and metastases. Clinicians should be aware of this entity as close follow-up is essential to detect recurrence and metastatic disease. Mohs micrographic surgery seems to result in superior patient outcomes.

The implicated clinical factors for outcomes in 304 patients with salivary duct carcinoma: Multi-institutional retrospective analysis in Japan.

BACKGROUND: Salivary duct carcinoma (SDC) is a high-grade salivary malignancy that frequently occurs as the carcinomatous component of carcinoma ex pleomorphic adenoma. We herein examined the clinical factors affecting outcomes in a large cohort of SDC. METHODS: We selected 304 SDC cases and investigated clinical characteristics and the factors affecting outcomes. RESULTS: The median age of the cases examined was 68 years, the most common primary site was the parotid gland (238 cases), and there was a male predominance (M/F = 5:1). Outcomes were significantly worse when the primary tumor site was the minor salivary glands (SG) than when it was the major SG. Outcomes were also significantly worse in pN(+) cases (161 cases) than in pN0 cases, particularly those with a metastatic lymph node number ≥11. The cumulative incidence of relapse and distant metastases was significantly higher in stage IV cases than in stage 0-III cases. CONCLUSIONS: The absolute number of lymph node metastases, higher stages, and the minor SG as the primary tumor site were identified as factors affecting the outcome of SDC.

Comparing the effect of distance to treatment facility on reconstruction and breast conservation therapy for early-stage invasive ductal carcinoma between the nation and the mountain region.

BACKGROUND: Our objective is to evaluate the effect of distance to facility on the use of breast conservation therapy and reconstruction for early stage breast cancer. METHODS: Utilizing the National Cancer Database, we identified females, age <65, with Stage I invasive ductal carcinoma from 2004 to 2015. Using logistic regression, we compared radiation, mastectomy, and reconstruction treatment patterns. A subgroup analysis was performed within the mountain region (MR). RESULTS: Nationwide, there are decreasing odds of radiation, increasing odds of mastectomy, and increasing odds of reconstruction. Patients living farther were less likely to receive radiation, more likely to undergo mastectomy, with no effect on reconstruction. Within the MR, patients living farther from their facility were less likely to receive radiation, more likely to undergo mastectomy, however, they were less likely to undergo reconstruction. CONCLUSIONS: Nationwide and within the MR, patients living farther from their facility are less likely to receive radiation and more likely to undergo mastectomy. There is a disparity between the MR and the nation in use of reconstruction for this population.

A rare case of malignant biliary stenosis due to retroperitoneal metastasis from breast invasive ductal carcinoma.

A 50-year-old woman was referred to our hospital for elevated hepatobiliary enzymes. She had a medical history of mastectomy for left breast invasive ductal carcinoma about 10 years ago, and no apparent recurrence had been observed. Contrast-enhanced computed tomography (CT) revealed soft-tissue shadows surrounding the portal vein, celiac artery, and other vessels. The lesions involved the hilar bile duct, and the upstream bile ducts were dilated. Endoscopic retrograde cholangiography showed an obstruction in the hilar bile duct, and biopsies were taken at the site of biliary stenosis. H&E staining showed that cells with strong nuclear atypia and prominent chromatin staining infiltrated in the stroma. Immunohistochemical analysis revealed that the cells were positive for CK7, GATA3 and weakly positive for CK20. Based on these results, we made the diagnosis of biliary stenosis due to retroperitoneal metastasis from breast invasive ductal carcinoma. Biliary inside stents were placed across the biliary stricture, and she received chemotherapy plus endocrine therapy for breast cancer. So far, the partial response has been maintained for 1 year since the diagnosis of retroperitoneal metastasis. Although retroperitoneal metastasis from breast cancer, especially breast invasive ductal carcinoma, is extremely rare, it could be a differential diagnosis for biliary stenosis.

Intraductal Carcinoma of the Prostate: Extreme Nuclear Size Is Not a Diagnostic Parameter.

High-grade prostatic adenocarcinoma involving duct/acinar structures is labeled intraductal carcinoma of the prostate (IDCP). As numerous studies have shown that IDCP is associated with high stage disease with a significant negative impact on cancer-specific survival, accurate diagnosis is crucial to ensure appropriate patient management. The definition of IDCP recommended by 2016 World Health Organization (WHO) classification suggests that cases of IDCP with micropapillary or loose cribriform architecture without comedonecrosis should have cells with ≥6× nuclear enlargement. It is unclear how this size criterion was derived and which of the parameters of nuclear size (nuclear diameter, nuclear surface area, or nuclear perimeter) it relates to. To evaluate the extent of nuclear enlargement in IDCP, we performed morphometric analyses relating to each of these parameters in 100 radical prostatectomy specimens. One hundred nuclei from foci of IDCP and 50 nuclei from foci of normal luminal epithelium were examined for each patient. Diagnosis of IDCP was based on cells with definite features of carcinoma present within duct/acinar structures. Comparing the means of each of the parameters between IDCP cells and benign luminal cells, there was a statistically significant enlargement in nuclear perimeter (P<0.0005), nuclear area (P<0.0005), and nuclear diameter (P<0.0005); however, the difference in mean nuclear size was limited to factors of 1.3×, 1.6×, and 1.3×, respectively. Three patients each had rare large nuclei (largest perimeter 45, 45, and 44 µm; maximum nuclear area 135, 136, and 136 µm2; and the largest diameter 18 µm in each). For these rare cells, the nuclear size difference, when compared with benign nuclei was; nuclear perimeter 2.0×, 2.1×, and 2.1×; nuclear area 3.6×, 3.8×, and 3.8×; and nuclear maximum diameter 3.0×, 2.5×, and 2.5×. The definition of nuclear enlargement of ≥6× was not reached in any of our cases, all of which clearly showed features of duct invasive carcinoma. In these cases, reliance on nuclear size criteria would have resulted in underdiagnosis of IDCP. This is of concern as failure to recognize IDCP, particularly in needle biopsies, could lead to delays in the timely treatment of aggressive high-grade prostate cancer, resulting in cancer progression and suboptimal patient oncological outcomes.

Establishment and characterization of a new spontaneously immortalized ER-/PR-/HER2+ human breast cancer cell line, DHSF-BR16.

Invasive ductal carcinoma (IDC) constitutes the most frequent malignant cancer endangering women's health. In this study, a new spontaneously immortalized breast cancer cell line, DHSF-BR16 cells, was isolated from the primary IDC of a 74-years old female patient, treated with neoadjuvant chemotherapy and disease-free 5-years after adjuvant chemotherapy. Primary breast cancer tissue surgically removed was classified as ER-/PR-/HER2+, and the same phenotype was maintained by DHSF-BR16 cells. We examined DHSF-BR16 cell morphology and relevant biological and molecular markers, as well as their response to anticancer drugs commonly used for breast cancer treatment. MCF-7 cells were used for comparison purposes. The DHSF-BR16 cells showed the ability to form spheroids and migrate. Furthermore, DHSF-BR16 cells showed a mixed stemness phenotype (i.e. CD44+/CD24-/low), high levels of cytokeratin 7, moderate levels of cytokeratin 8 and 18, EpCAM and E-Cadh. Transcriptome analysis showed 2071 differentially expressed genes between DHSF-BR16 and MCF-7 cells (logFC > 2, p-adj < 0.01). Several genes were highly upregulated or downregulated in the new cell line (log2 scale fold change magnitude within - 9.6 to + 12.13). A spontaneous immortalization signature, mainly represented by extracellular exosomes-, plasma membrane- and endoplasmic reticulum membrane pathways (GO database) as well as by metabolic pathways (KEGG database) was observed in DHSF-BR16 cells. Also, these cells were more resistant to anthracyclines compared with MCF-7 cells. Overall, DHSF-BR16 cell line represents a relevant model useful to investigate cancer biology, to identify both novel prognostic and drug response predictive biomarkers as well as to assess new therapeutic strategies.

Ductal variant prostate carcinoma is associated with a significantly shorter metastasis-free survival.

BACKGROUND: Ductal adenocarcinoma is an uncommon prostate cancer variant. Previous studies suggest that ductal variant histology may be associated with worse clinical outcomes, but these are difficult to interpret. To address this, we performed an international, multi-institutional study to describe the characteristics of ductal adenocarcinoma, particularly focussing on the effect of presence of ductal variant cancer on metastasis-free survival. METHODS: Patients with ductal variant histology from two institutional databases who underwent radical prostatectomies were identified and compared with an independent acinar adenocarcinoma cohort. After propensity score matching, the effect of the presence of ductal adenocarcinoma on time to biochemical recurrence, initiation of salvage therapy and the development of metastatic disease was determined. Deep whole-exome sequencing was performed for selected cases (n = 8). RESULTS: A total of 202 ductal adenocarcinoma and 2037 acinar adenocarcinoma cases were analysed. Survival analysis after matching demonstrated that patients with ductal variant histology had shorter salvage-free survival (8.1 versus 22.0 months, p = 0.03) and metastasis-free survival (6.7 versus 78.6 months, p < 0.0001). Ductal variant histology was consistently associated with RB1 loss, as well as copy number gains in TAP1, SLC4A2 and EHHADH. CONCLUSIONS: The presence of any ductal variant adenocarcinoma at the time of prostatectomy portends a worse clinical outcome than pure acinar cancers, with significantly shorter times to initiation of salvage therapies and the onset of metastatic disease. These features appear to be driven by uncoupling of chromosomal duplication from cell division, resulting in widespread copy number aberration with specific gain of genes implicated in treatment resistance.