Triple Negative Invasive Carcinoma Research Articles

Tall Cell Variant of Invasive Papillary Breast Carcinoma.

Tall cell variant of invasive papillary breast carcinoma is exceedingly rare, with only 30 cases reported in the literature. This report describes a case of a 47-year-old woman who presented to the clinic with bilateral breast masses on a screening mammogram. The patient was lost to follow-up, but she presented again after 4 years when the right breast mass significantly grew in size over several months. Mammography showed a 1.9 cm right breast mass and a 2.3 cm left breast mass. Ultrasound-guided core biopsy revealed right breast triple negative invasive carcinoma of the tall cell papillary variant and left breast fibroadenomatoid nodules. She underwent bilateral lumpectomies with a right sentinel lymph node biopsy and was started on chemotherapy after surgical excision.

Metastatic adenocarcinoma to the breast from the lung simulates primary breast carcinoma—a clinicopathologic study

BackgroundRare extra-mammary metastases of adenocarcinoma to the breast closely mimic primary invasive breast carcinoma (PBC), and specifically without an aware of clinical history, pose a difficult diagnostic issue.MethodsWith the aim to improve differential diagnosis of lung adenocarcinoma metastasis and primary breast carcinoma in the breast, we retrieved 41 breast metastases from lung adenocarcinoma, seven of which were from the archived pathologic files of Cancer Hospital, Chinese Academy of Medical Science (CHCAMS) between 2001 and 2019, and the other 34 cases were collected from the published literatures. Clinicopathological features were collected and analyzed for differential diagnosis of primary lung malignancy, triple negative breast pathology and breast lesions without ipsilateral axillary lymphadenopathy or with contralateral axillary lymphadenopathy. Supplementary breast (GCDFP-15, or GATA-3) and lung-lineage (TTF-1) immunostaining plus genetic alternation analysis were also recorded and analyzed.ResultsAmong the 41 cases, there were 37 females and four males, with a median age of 63 (range, 40–81) years at diagnosis of the breast lesion. Twenty-four cases (58.5%, 24/41) were detected metachronously to the counterpart of the lung. Strikingly, 13 cases (31.7%, 13/41) were initially misdiagnosed as primary breast cancer, and differential diagnostic factors were compared and analyzed between the correct and misdiagnosed cases, among which a documentation of lung cancer history showed significant difference. Pathologist initially misinterpreted six cases (46.2%, 6/13) as PBC on needle biopsy of breast mass with an unknown lung cancer history. The clinical diagnosis was considered two cases (15.4%, 2/13) to be either a primary breast tumor with lung and pleural metastasis or two synchronous primary tumors. Three cases (23.1%, 3/13) were initially misinterpreted as PBC by breast ultrasonography. TTF-1 immunostaining was found to be critical for a correct diagnosis of metastatic lesion (84.6%, 11/13) from the initially misdiagnosed cases as PBC.ConclusionsMetastatic lung adenocarcinoma to the breast, although rare, should be considered in the differential diagnosis of primary breast carcinoma, especially when the breast lesion exhibits as a “triple-negative invasive carcinoma”. A documented lung cancer history combined with the clinicoradiological assessment and pathological evaluation are essential to make a correct differential diagnosis. TTF-1 immunostaining is crucial in approaching the diagnosis.

SUN-927 Ectopic Cushing Syndrome Due to a Metastatic Neuroendocrine Tumor to the Breast

Introduction:We present a rare case of ectopic Cushing syndrome (CS) due to a neuroendocrine tumor (NET) metastatic to the breast.Case:A 38-year-old female was referred for ACTH-dependent CS. She had rapid development of cushingoid features and hypertension three months prior to presentation. A 24-hour urinary free cortisol (UFC) was elevated to 2548 μg (0-50 μg/24hr), and ACTH was 228 pg/mL (10-60 pg/mL). A pituitary MRI was normal, and inferior petrosal sinus sampling was not consistent with a central ACTH source. A DOTA-TATE scan showed mediastinal lymphadenopathy and a 0.8cm area of uptake in the right breast. The patient was placed on ketoconazole and UFC normalized. Following biopsy, she underwent breast lumpectomy at an outside hospital, and pathology showed triple negative invasive carcinoma of the breast. Chemotherapy was initiated.However, her CS rapidly worsened: repeat UFC was 4867 μg, and ACTH was 369 pg/mL. Re-review of her pathology slides at our facility showed that the tumor stained negative for breast markers and positive for markers of NET and ACTH. Ki67 staining was approximately 30%. Chemotherapy for breast cancer was immediately stopped. A follow-up PET-CT continued to show uptake in the mediastinal lymph nodes. FNA of these lymph nodes revealed metastatic NET. In order to maximize control of her CS prior to chemotherapy, she underwent bilateral adrenalectomy (BLA). Afterwards, the patient received 10 cycles of chemotherapy with modified FOLFOX-7 for her NET. Thus far, the tumor burden appears stable, and she has been recommended to hold off on radiation therapy. She is currently taking replacement doses of hydrocortisone and fludrocortisone.Conclusion:In this challenging case, determination of source of ACTH hypersecretion led to an initial diagnosis of breast cancer. Primary breast carcinoma with neuroendocrine differentiation has been reported to show significant overlap in pathology with NET metastatic to the breast1. However, worsening of the CS in this case led to consideration of an alternative diagnosis, resulting in diagnosis of an ACTH producing NET metastatic to the breast. Prior to chemotherapy, she underwent BLA, which may lower morbidity and mortality associated with ACTH-dependent CS2, particularly given plan for further chemotherapy.Reference:1. Mohanty SK, Kim SA, DeLair DF, et al. Comparison of metastatic neuroendocrine neoplasms to the breast and primary invasive mammary carcinomas with neuroendocrine differentiation. Mod Pathol. 2016;29(8):788-798. doi:10.1038/modpathol.2016.69.2.2. Morris LF, Harris RS, Milton DR, et al. Impact and timing of bilateral adrenalectomy for refractory adrenocorticotropic hormone-dependent Cushing’s syndrome. Surgery. 2013;154(6):1174-1183; discussion 1183-1184.

Management and prognosis of pure primary squamous cell carcinoma of the breast

PurposeThe aim of the study was to investigate the management and prognosis of Pure primary squamous cell carcinoma (PPSCC) of the breast. Materials and methodsThis study is a multicentre retrospective cohort from three French tertiary referral hospitals (Rennes, Orléans and Tours) including all women treated for a PPSCC of the breast defined by squamous cells that could contain a minority of sarcomatoid component. We excluded carcinomas with a ductual component. Clinicopathologic, radiological and therapeutic patterns were described. Demographic, histological and therapeutic characteristics were compared to a population of women with triple negative invasive breast carcinomas. ResultsTwelve patients were included, with a mean age of 71.6 years. All lesions were unifocal, with a cystic complex ultrasound mass in 50% of cases. Mean tumor size was 43mm, with axillary lymph node metastasis in 25% of patients.The comparison with a population of women with triple negative breast carcinomas revealed that women with PPSCC were older (71 versus 57 years, p=0.003), tumor size was larger (43mm versus 25mm, p=0.032) and local recurrence occurred earlier (three months versus 38 months, p=0.014). ConclusionPPSCC is a rare entity with a worse prognosis in comparison with triple negative invasive carcinoma.

Immunohistochemical features of claudin-low intrinsic subtype in metaplastic breast carcinomas

PurposeThe claudin-low molecular subtype of breast cancer includes triple negative invasive carcinomas, with a high frequency of metaplastic and medullary features. The aim of this study was to evaluate the immunohistochemistry expression of claudins in a series of metaplastic breast carcinomas. We also assessed other claudin-low features, such as the cancer stem cell-like and epithelial-to-mesenchymal transition phenotypes. ResultsThe majority of the cases showed weak or negative staining for membrane claudins expression. We found 76.9% (10/13) low expressing cases for claudin-1, 84.6% (11/13) for claudin-3 and claudin-4, and 92.3% (12/13) for claudin-7. Regarding the cancer stem cell marker ALDH1, 30.8% (4/13) showed positive staining. We also showed that the majority of the cases presented a CD44+CD24−/low phenotype, positivity for vimentin and lack of E-cadherin expression. Interestingly, these claudin-low molecular features were specific of the mesenchymal component of metaplastic breast carcinomas, since its frequency was very low in other breast cancer molecular subtypes, as luminal, HER2-overexpressing and non-metaplastic triple negative tumors. ConclusionsThe negative/low expression of claudins and E-cadherin, high levels of vimentin, and the breast cancer stem cell phenotype suggests that metaplastic breast carcinomas have similar features to the ones included in the claudin-low molecular subtype, specially their mesenchymal components.

Immunophenotypes of Glycogen Rich Clear Cell Carcinoma

PurposeGlycogen rich clear cell carcinoma (GRCC) of the breast is a rare subtype of invasive ductal carcinoma and involves a poor prognosis. In the literature, less than 150 cases have been reported. Many researchers have attempted to characterize GRCC according to electron microscope, flow cytometry, or clinical data. However, an organized study of the immunophenotype of GRCC has yet to be reported.Materials and MethodsHere, we present three cases of GRCC and their immunohistochemical profiles.ResultsHistologically, all three cases contained periodic acid stain (PAS) positive and d-PAS labile granules in their clear cytoplasm. Case I showed positivity for only estrogen receptor (ER) and c-erbB2. Case II exhibited positivity for progesterone receptor and negativity for ER and c-erbB2. Case III presented with triple negative invasive carcinoma. The expression pattern of E-cadherin was concordant with epidermal growth factor receptor and c-kit, but discordant with ki-67. Among these three cases, p53-positive cases exhibited a low proliferative index (ki-67: 15%), while p53-negative cases showed a high proliferative index (ki-67: 50-60%).ConclusionIn conclusion, the immunophenotype of GRCC is not uniform, but is similar to that of conventional ductal carcinoma.

Clinical outcome of triple-negative primary breast cancer in older women: Comparison with their younger counterparts.

1057 Background: It is generally believed that triple-negative (ER-/PR-/HER2-) primary breast cancers have poor prognosis. Following surgery, adjuvant chemotherapy is currently the only treatment that could potentially improve survival. On the other hand, the absolute benefit of adjuvant chemotherapy in older women appears small and its precise value remains to be proven. As such its use tends to be very limited in this population. Methods: Over 36 years (1973−2009), 2,000+ older (≥70 years) women with early operable primary breast cancer were managed in a dedicated clinic. Of these 127 patients with triple negative invasive carcinoma (defined as ER/PR = 0% positive cells, HER2 = 1+ or 2+ on IHC and CISH negative) underwent primary surgery and had good quality tumour samples available for tissue microarray (TMA) analysis using indirect immunohistochemistry. The results were compared with their younger (<70 years) counterparts from a previously characterised, consecutive series (N=1,809) treated in the same unit (1986–1998). Among them, there were 342 patients who had triple negative tumors. Results: At a median follow-up of 46 months (longest=204) (≥70 years) and 119 months (longest=135) (<70 years), the results are shown in the table. Conclusions: Despite not having received adjuvant chemotherapy, the older series had clinical outcome similar to the younger patients almost half of which had chemotherapy. This may be due to other biomarkers (in addition to ER/PR/HER2) which have different patterns in these age groups influencing prognosis. The place of adjuvant chemotherapy in the treatment of these patients has yet to be identified. Treatment pattern <70 years ≥70 years With adjuvant chemotherapy 149 (47.0%) 0 Without adjuvant chemotherapy 168 (53.0%) 127 (100%) Outcome at 5 years P value Breast cancer-specific survival 73% 79% 0.39 Local recurrence 10% 14% 0.16 Regional recurrence 11% 14% 0.40 Metastases 30% 27% 0.56

Triple‐negative breast cancer: Histological subtypes and immunohistochemical and clinicopathological features

To reveal heterogeneous properties of triple-negative (TN) breast cancers (estrogen receptor negative, progesterone receptor negative and HER2 negative) and to clarify whether the developmental pathways to TN breast cancer are single or multiple, we conducted clinicopathological and immunohistochemical studies on TN breast cancers, with special reference to comparison of the invasive component (iIC) and the ductal component (dcIC) of invasive TN breast cancer and pure TN ductal carcinoma in situ (TNDCIS). Tumor tissues were obtained from 97 patients with TN invasive carcinoma and 10 patients with TNDCIS. Two histological subclassifications, "atypical" medullary carcinoma (type A, n=16) and carcinoma with a central acellular zone (type B, n=11), were distinguished from conventional ductal carcinoma. Other invasive ductal carcinomas were classified as type C (n=64) and special types were classified as type D (n=5). The follow-up period for the 96 patients ranged from 5 to 147.8 months (mean, 47.6 months). Out of 97 cases, dcIC was present in 29 (30%) cases and type A and B had significantly few ductal components, 0% and 18%, respectively. There were only six (6%) cases with non-TN cells in dcIC and TN cells in iIC and five of them were type C. In 13 (13%) cases, epidermal growth factor receptor (EGFR) expression existed only in iIC. Therefore, most of the TN carcinoma develops originally and rapidly invades at the early stage, especially in types A and B. The relapse rate of type B was the highest (36.4%) and the overall survival of patients with type B was the shortest (P=0.02), which indicates that the prognosis of type B is significantly worse than the other types.

Abstract P6-01-04: Ductal Carcinoma In-Situ Associated with Triple-Negative Invasive Breast Carcinoma Is Often Immunohistochemically Distinct from Invasive Component

Abstract Background: Gene expression profiling studies have identified a sub-set of breast carcinoma known as basal-like carcinoma, which characteristically do not express estrogen receptor (ER), progesterone receptor (PR), or HER2neu (HER2). These triple negative invasive ductal carcinomas (TN-IDC) are associated with an aggressive clinical course and poor prognosis. Little information exists in the literature concerning ductal carcinoma in-situ (DCIS) associated with TN-IDC. We evaluated the frequency, histologic features, and receptor status of DCIS associated with TN-IDC. Design: From our institutional archives between July 2006 and August 2009, we retrieved all cases of intermediate and high grade invasive ductal breast carcinoma. Based on the immunoprofiling, invasive carcinomas were categorized into either TN-IDC or non triple-negative invasive carcinoma (non-TN-IDC). Immunohistochemistry for ER, PR, and HER2 was performed on the DCIS of the TN-IDC group and on some available cases from the non-TN-IDC group. The frequency, receptor status, and nuclear grade of DCIS associated with both groups were noted. Statistical analysis was performed using Fisher Exact Test. Results: Among a total of 224 cases, 56 (25%) were classified as TN-IDC and 168 (75%) as non-TN-IDC. DCIS was seen in 28 (50%) TN-IDC cases and in 150 (89.3%) non-TN-IDC cases (P&amp;lt;0.0001). Sufficient tumor was available for immunohistochemical staining in 23 of 28 cases with DCIS in the TN-IDC group. Within the 23 cases, the DCIS were triple negative in 15 cases (65%). Of the remaining 8 cases (35%), 4 were positive for ER and PR, but negative for HER2, while the other 4 cases were negative for ER and PR but positive for HER2. Ninety-six cases in the non-TN-IDC group had available immunostains for review, 7 of which (7.3%) displayed a different receptor status from their invasive counterparts (p=0.0016, compared with TN-IDC). Two cases of non-TN-IDC showed an associated TN-DCIS. Of the 28 cases of TN-IDC associated with DCIS, 4 (14.3%) showed lower nuclear grade in DCIS than in its invasive counterpart, compared with 22 of 150 (14.7%) non-TN-IDC cases (no significant difference). One TN-IDC case displayed two distinct morphologic patterns of DCIS; neither pattern was triple negative. Conclusion: Our study demonstrated the presence of DCIS in a considerable proportion of TN-IDC although at a significantly lower frequency than in non-TN-IDC. DCIS associated with TN-IDC was significantly more likely to display a different immunoprofile from its invasive counterpart than DCIS associated with non-TN-IDC. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-01-04.