Metastasis Of Lobular Breast Carcinoma Research Articles

Abstract PS19-06: Role of the calcium-sensing receptor (CaSR) in invasive lobular breast carcinoma metastasis to the ovary

Abstract Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer, after the more common invasive ductal carcinoma (IDC). ILC accounts for 10 to 15% of all invasive breast carcinomas, affecting approx. 26,000-40,000 women in 2020 in the US alone. Despite 95% of ILC being Luminal A conferring patients a favorable prognosis, patients with ILC have poorer long-term outcomes when compared to patients with Luminal A IDC. ILC spread to common sites of ER+ breast cancer metastasis such as the bones, but are also three times more likely to spread to the ovaries, peritoneum, and gastrointestinal tract compared to IDC, and these unique aspects of metastases remain poorly understood. To better understand metastasis to the ovary we performed DNA and RNA sequencing of 11 pairs of primary breast tumor and ovarian metastasis as well as 13 orphan breast cancer ovarian metastases. Our cohort was enriched for lobular histology, with 13 samples originating from ILC, 6 from IDC and 6 from mixed ILC/IDC. We found mutations in CDH1 (43%), PIK3CA (40%), and FOXA1 (29%) highlighting the enrichment in ILC cases present in our cohort. Gene expression analysis lead to identification of 874 differentially expressed between primary tumors and ovarian metastases. We identified the calcium-sensing receptor CaSR as one of the top upregulated in ovarian metastases compared to primary tumor in 10 out of the 11 paired samples. Other genes highly expressed in ovarian metastases included TAC3, GLRA2, ALLC, MUC19, CHRNA2, PIP, CST4, and TEX15. Pathways analyses showed an enrichment of signaling through glutamate receptor and glycine receptor families. To assess the contribution of CaSR to breast cancer cell proliferation and metastatic properties, and due to the absence of breast cancer cell lines expressing CaSR, we generated CaSR overexpression models using lentiviral infection in MDA-MB-134, MDA-MB-330, BCK4 and SUM44PE ILC cell lines. While overexpression of CaSR alone did not confer a cell growth advantage or migratory ability to the cell lines, stimulation with calcium or a calcium mimetic resulted in enhanced migration in transwell assays in 3 of the 4 cell lines. Scratch assays further confirmed the stimulation of cell migration in cells with CaSR overexpression in the presence of calcium. Cell migration in CaSR overexpression models could be stimulated with the calcimimetic R568, and inhibited by the calcilytics NPS2143, and F-actin staining confirmed the need to activate the receptor to enhance migratory properties. Our studies further revealed that the induced migratory properties of CaSR overexpressing cells required estradiol and ER signaling, and that migration could be blocked with ER inhibitors such as ICI 182,780 and tamoxifen. Western blotting data revealed that the enhanced cell migratory properties of CaSR overexpressing cells was via activation of the MEK/ERK pathway and migration could be inhibited using specific small molecule pathway inhibitors.Altogether, our study provides insight on the potential mechanism by which upregulation of the CaSR supports breast cancer ovarian metastasis. We hope that these studies will not only deepen our understanding of ILC ovarian metastasis but will eventually lead to the development of more effective therapies and improve the outcome of patients with this understudied type of breast cancer. Citation Format: Ye Qin, Laura Savariau, Ahmed Mohammed Basudan, Osama Shah, Zheqi Li, Tiantong Liu, Nilgun Tasdemir, Lan Coffman, Esther Elishaev, Jennifer M Atkinson, Peter Lucas, Adrian V Lee, Steffi Oesterreich. Role of the calcium-sensing receptor (CaSR) in invasive lobular breast carcinoma metastasis to the ovary [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS19-06.

Metastatic Lobular Breast Cancer Mimicking Colitis

Breast cancer is the most frequent cancer diagnosed in women in the world regardless of race or ethnicity. About 10% of invasive breast carcinomas are lobular subtype. The loss of the E-caderin expression that occurs in lobular carcinoma leads to a higher risk of metastases in membranes (meningeal, pleural, peritoneum) and gastrointestinal and/or endobronchial mucous, which may lead to several odd symptomatology. We report a 79 years old female patient with lobular breast cancer associated to CDH1 germline mutation. She was diagnosed with breast cancer in December 2016 after noticing a right-armpit nodule whose pathological examination demonstrated an immunohistochemistry profile compatible with lobular breast carcinoma metastasis and had estrogen receptors 98%, progesterone receptors < 1%, ki67 25%, negative her2 score. Family history of only one paternal uncle with stomach cancer. After two lines of hormone therapy, she had disease progression and started oral chemotherapy with capecitabine. In a few weeks, the patient had refractory diarrhea. At the beginning, it was defined like colitis chemotherapy related. However, the clinical features showed necessity of further investigation. Then, she was diagnosed with CDH1 germline mutation after massive progression at gastrointestinal mucous. This case made possible to inform the family about risk of germline mutation and necessity of genetic counseling.

Metastasis of lobular breast carcinoma in the bowel

Metastasis of lobular breast carcinoma in the bowel

Gastrointestinal metastases from breast cancer: A case report

Background Breast cancer is the most common type of cancer in women nowadays. According to published major studies, the most common sites of metastases of breast cancer are bone, lung, liver and brain. However, it can also metastasize rarely to the gastrointestinal tract. Among the different subtypes of breast cancer, gastrointestinal spread has been associated to infiltrating lobular carcinoma. We present a case of perforated acute diverticulitis that underwent surgery, in which the pathological exam informed of colonic metastasis of lobular breast carcinoma. Case report A 78-year-old woman, with medical history of high blood pressure, diabetes and left mastectomy performed 14 years ago for infiltrating lobular carcinoma (Stage T2N2M0), with positive estrogenic receptors. Oncological controls showed pleural and bone progression in the last year, so hormonal therapy was indicated. She was admitted to the emergency department due to 72 hours of left lower-quadrant abdominal pain associated with constipation and nausea. On examination she presented tenderness and a palpable mass in the left lower quadrant. Blood tests showed an increased leukocyte count of 13.5x103/µL with neutrophilia, a CRP of 356mg/L and high lactate levels (4.5mmol/L). An abdominal computed tomography (CT) scan showed a left inguinal abscess (6x8x7cm) communicating with an inflammatory mass involving the sigmoid colon, as well as extensive bone metastases, not visualized in previous CTs. An emergency Hartmann's procedure was performed. The postoperative period was uneventful. The pathological report of the surgical specimen informed of infiltration in multiple diverticula by a carcinoma, with morphological pattern and immunohistochemistry compatible with a lobular breast carcinoma. The patient was derived to the Department of Oncology to continue follow-up and hormonal therapy. Conclusions Gastrointestinal breast metastases are uncommon, however, we should consider this diagnosis in patients with tumoral progression presenting with abdominal symptoms. Metastatic patients should receive medical treatment, reserving surgery for complications like obstruction or perforation, as in the case presented.

Metastasis of breast cancer to an endometrial polyp, the cervix and a leiomyoma: A case report and review of the literature.

Haematogenous metastases of breast cancer tumors has previously been demonstrated to frequently occur at the sites of the lung, bones, liver and brain, however presence in the uterine remains a rare occurrence. Metastatic carcinoma of the uterus usually originates from other genital sites, most frequently from the ovaries. The current review presents the first reported case of lobular breast carcinoma metastasizing to an endometrial polyp, the cervix and a leiomyoma simultaneously. The patient (58 years, female) first presented with abnormal uterine bleeding. Invasive ductal carcinoma had previously been diagnosed in her right breast, with lobular and ductal cancer cells observed to be present in her lymph nodes. A hysteroscopic procedure to examine the postmenopausal bleeding revealed an endometrial polyp, which was subsequently resected. The morphology and immunohistochemical studies confirmed the diagnosis of metastasis of lobular breast carcinoma to an endometrial polyp. An 18F fludeoxyglucose positron emission tomography/computed tomography (PET-CT) scan performed following the diagnosis, revealed a slightly increased uptake in the myoma, which is often observed in benign uterine leiomyoma. The patient then underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy and partial colectomy. Pathology results demonstrated that the uterine leiomyoma and cervix shared the same histopathological features as those presented by the primary lobular breast carcinoma. Although rare, breast tumors may metastasize to an endometrial polyp, cervix and leiomyoma concurrently in patients, therefore physicians may now consider the potential of the diagnosis of metastatic spread to the genital tract, in a patient with abnormal uterine bleeding and a history of lobular breast cancer. Gynecologists planning a laparoscopic hysterectomy for a patient with a history of lobular breast carcinoma may consider abdominal rather than laparoscopic hysterectomy, as lobular carcinoma is difficult to detect. The use of PET-CT may be beneficial for the identification of an unexpected mass.

Gallbladder metastasis of lobular breast carcinoma

Gallbladder metastasis of lobular breast carcinoma

Diarrhoea Caused by Diffuse Metastatic Lobular Breast Cancer.

A 70-year-old woman with a history of lobular breast cancer presented to our Outpatient Clinic with diarrhoea for the past 3 years. Clinical examination and laboratory research were normal. Colonoscopy showed diffuse mild erythema and a decreased vascular pattern. Biopsies from the ascending colon, transverse colon, and descending colon showed metastases of lobular breast carcinoma. Although gastrointestinal metastases are rare in breast cancer, our case emphasizes the need for further diagnostic efforts in patients with gastrointestinal symptoms and a history of breast carcinoma.

α-Parvin, a pseudopodial constituent, promotes cell motility and is associated with lymph node metastasis of lobular breast carcinoma

Invasive lobular carcinoma (ILC) is more frequently lymph node positive than is invasive ductal carcinoma (IDC), and ILC cell infiltration shows distinctive histological characteristics, suggesting the action of ILC-specific invasion molecules. To identify such a molecule, we used a proteomic approach in the pseudopodia of MDA-MB-231 breast cancer cells. A pseudopodial constituent was identified using excimer laser ablation, two-dimensional difference gel electrophoresis, mass spectroscopy, and immunocytofluorescence. MDA-MB-231 cells were modified to express various levels of this constituent by transient transfection and were examined for pseudopodia formation and migratory abilities using wound healing and two-chamber assays. Immunohistochemical positivity of human breast cancer cells (56 ILCs and 21 IDCs) was compared with clinicopathological variables. An actin-binding adaptor protein, α-parvin, was found to localize to pseudopodia and to form focal adhesions in cells not induced to extend pseudopodia. Pseudopodial length and density and migratory abilities correlated with α-parvin expression. Twenty-one (37.5 %) ILCs stained positive for α-parvin, whereas the results were negative for all 21 IDCs (P < 0.001). α-Parvin positivity in ILC was significantly associated with lymphatic invasion (P = 0.038) and lymph node metastasis (P = 0.003) in univariate analyses and to lymph node metastasis (P = 0.020) in multivariate analyses. α-Parvin, a pseudopodial constituent, was found to promote migration of breast cancer cells and to be expressed exclusively by ILC, suggesting that α-parvin is an ILC-specific invasion molecule that may have clinical utility as a biomarker for aggressive subsets of ILC.

Synchronous Metastasis From Lobular Carcinoma and Primary Carcinoma of the Endometrium in a Patient After Tamoxifen Therapy

Patients treated with tamoxifen often experience vaginal bleeding, generally because of benign endometrial lesions or, less often, because of endometrial carcinoma. A rare cause of vaginal bleeding in these patients is breast carcinoma metastasis in an endometrial polyp. We describe a 67-yr-old patient with metastasis of lobular breast carcinoma in an endometrial polyp and papillary serous endometrial carcinoma, both diagnosed simultaneously in a uterine curettage. The coexistence of the 2 cancers was confirmed by pathologic study of the hysterectomy specimen. To our knowledge, this is the first reported case of the synchronous presence of the 2 neoplastic diseases. Endometrial biopsies performed for endometrial disorders in patients who have breast cancer and have received tamoxifen should be studied carefully to avoid underdiagnosis.

Lobular Breast Carcinoma Metastasis to a Superficial Plexiform Schwannoma as the First Evidence of an Occult Breast Cancer

Tumor to tumor metastasis is a rare phenomenon, in which one, benign or malignant, tumor is involved by metastatic deposits from another. Most documented tumor to tumor metastases have been located intracranially, in which, in the majority of cases, either a breast or a lung carcinoma metastasized to a meningioma. Only 7 cases of metastases to schwannoma have so far been reported in the English literature, in 6 cases to an intracranial acoustic schwannoma and in a single case to a subcutaneous schwannoma. We present a case of dermal/subcutaneous plexiform schwannoma containing metastatic deposits of an occult lobular breast carcinoma, creating a unique schwannoma with epithelioid cells. Differential diagnosis of schwannoma with epithelioid cells includes malignant transformation of schwannoma and metastasis of a carcinoma or melanoma to schwannoma, epithelioid schwannoma, and schwannoma with glandular or pseudo glandular elements.

Metastasis of lobular breast carcinoma diagnosed by rectal macrobiopsies

Metastasis of lobular breast carcinoma diagnosed by rectal macrobiopsies

Carcinome apocrine cutané axillaire inhabituel : difficultés diagnostiques histologiques

Apocrine carcinoma of the skin (ACS) is a rare adnexal neoplasm presenting as an indurated slow-growing dermal or subcutaneous plaque that often occurs in the axilla. Histological distinction between ACS and cutaneous metastases of breast carcinoma may be difficult. A 64-year-old man presented with a slowly growing left axillary mass, which he had noticed for 2 years, without any other functional or clinical symptoms. Histological examination of the skin biopsy showed dermal invasion with atypical cells in an "Indian file" pattern. The pattern of the tumour and immunohistochemical staining suggested a diagnosis of breast carcinoma metastasis. However, the history of a slow-growing tumour and negative initial testing for a primary adenocarcinoma supported the hypothesis of ACS. A 100 cases of ACS have been reported in the literature with the main site being the axillary area. The differential diagnostic between axillary ACS and metastasis of lobular breast carcinoma has been discussed recently. Diagnosis may be difficult since the pattern of the tumour can be misleading and immunomarkers are not always specific. We report a new case of axillary ACS histologically mimicking lobular breast carcinoma metastasis.

Esophageal Stricture Due to Intramural Metastases of Lobular Breast Carcinoma

Esophageal Stricture Due to Intramural Metastases of Lobular Breast Carcinoma

Metastasis of lobular breast carcinoma to the cervix

Breast cancers without previous dissemination occasionally result in hematogenous metastases in gynecologic organs, particularly in the cervix. This case report examines a multimodally treated lobular breast cancer patient who was 52 months later diagnosed with malignancy in the uterus. After a tumor was detected at the endocervical and isthmic part of the uterus, a complete hysterectomy with bilateral salpingo-oophorectomy was carried out. The malignant cells were highly positive for carcino-embrional antigen and gross cystic disease fluid protein-15, sensitive breast cancer markers. In conclusion, as breast carcinoma can metastasize to atypical places (cervix, endometrium, etc.), regular surveillance of patients should include gynecologic control.