Medullary Carcinoma Of Breast Research Articles

2005: Long-Term Outcome in Patients With Early Stage Tubular, Medullary and Colloid Breast Carcinoma Treated With Breast Conservation Therapy

To evaluate the characteristics and long-term outcome of pts with early stage tubular, medullary and colloid breast carcinoma compared to other invasive ductal histology (IDC) treated with conservative surgery and radiation (RT).

2–39 Clinicopathologic Features and Long-Term Outcome of Patients With Medullary Breast Carcinoma Managed With Breast-Conserving Therapy (BCT)

2–39 Clinicopathologic Features and Long-Term Outcome of Patients With Medullary Breast Carcinoma Managed With Breast-Conserving Therapy (BCT)

Carcinoma medular de mama: una lesión maligna que simula benignidad

Medullary carcinoma of the breast is an unfrequent type of tumor. We present a case of medullary carcinoma of the breast. The patient presented with a palpable breast mass, corresponding on mammography to an obscured mass, which showed a cystic appearance with thick wall on sonography. We review the radiological findings of this type of tumor which should be considered in the differential diagnosis of lesions with well-circumscribed margins.

Medullary breast carcinoma: A case report with cytological features and histological confirmation

We report the case of a 83-year-old woman who presented with a left-breast lump. On physical examination the patient had a well-demarcated mass located in the upper outer quadrant of her left breast with a palpable unilateral axillary lymph node. Mammography and ultrasonography depicted a heterogeneous well-defined lesion measuring 6 cm in diameter without calcifications. Fine-needle aspiration cytology of the lesion was performed. Cytological examination revealed highly cellular smears containing large atypical cells arranged in syncytial sheets and intimately admixed with lymphocytes and neutrophils. The nuclear to cytoplasmic ratio was high in tumor cells whose nucleus exhibited coarse chromatin with one or more conspicuous nucleoli. The diagnosis of medullary breast carcinoma, which was strongly suspected by cytology, was confirmed by histological examination of the surgical specimen after a modified radical mastectomy with axillary dissection.

397 PUBLICATION Outcome of node-negative mucinous, medullary and tubular breast carcinoma

397 PUBLICATION Outcome of node-negative mucinous, medullary and tubular breast carcinoma

Novel Ganglioside Antigen Identified by B Cells in Human Medullary Breast Carcinomas: The Proof of Principle Concerning the Tumor-Infiltrating B Lymphocytes

The potential tumor-recognizing capacity of B cells infiltrating human breast carcinoma is an important aspect of breast cancer biology. As an experimental system, we used human medullary breast carcinoma because of its heavy B lymphocytic infiltration paralleled to a relatively better prognosis. Ig-rearranged V region V(H)-J(H), Vkappa-Jkappa, and Vlambda-Jlambda genes, amplified by RT-PCR of the infiltrating B cells, were cloned, sequenced, and subjected to a comparative DNA analysis. A combinatorial single-chain variable fragment Ab minilibrary was constructed out of randomly selected V(H) and Vkappa clones and tested for binding activity. Our data analysis revealed that some of the V(H)-J(H), Vkappa-Jkappa, and Vlambda-Jlambda region sequences were being assigned to clusters with oligoclonal predominance, while other characteristics of the Ab repertoire were defined also. A tumor-restricted binder clone could be selected out of the single-chain variable fragment kappa minilibrary tested against membrane fractions of primary breast tumor cells and tumor cell lines, the V(H) of which proved to be the overexpressed V(H)3-1 cluster. The specific binding was confirmed by FACS analysis with primary breast carcinoma cells and MDA-MB 231 cell line. ELISA and thin layer chromatography dot-blot experiments showed this target Ag to be a ganglioside D3 (GD3). Our results are a proof of principle about the capacity of B cells infiltrating breast carcinomas to reveal key cancer-related Ags, such as the GD3. GD3-specific Abs may influence tumor cell progression and could be used for further development of diagnostic and/or therapeutic purposes.

High proportion of recurrent germline mutations in the BRCA1 gene in breast and ovarian cancer patients from the Prague area

BackgroundGermline mutations in the BRCA1 and BRCA2 genes have been shown to account for the majority of hereditary breast and ovarian cancers. The purpose of our study was to estimate the incidence and spectrum of pathogenic mutations in BRCA1/2 genes in high-risk Czech families.MethodsA total of 96 Czech families with recurrent breast and/or ovarian cancer and 55 patients considered to be at high-risk but with no reported family history of cancer were screened for mutations in the BRCA1/2 genes. The entire coding sequence of each gene was analyzed using a combination of the protein truncation test and direct DNA sequencing.ResultsA total of 35 mutations in the BRCA1/2 genes were identified in high-risk families (36.5%). Pathogenic mutations were found in 23.3% of breast cancer families and in 59.4% of families with the occurrence of both breast and ovarian cancer. In addition, four mutations were detected in 31 (12.9%) women with early onset breast cancer. One mutation was detected in seven (14.3%) patients affected with both a primary breast and ovarian cancer and another in three (33.3%) patients with a bilateral breast cancer. A total of 3 mutations in BRCA1 were identified among 14 (21.4%) women with a medullary breast carcinoma. Of 151 analyzed individuals, 35 (23.2%) carried a BRCA1 mutation and 9 (6.0%) a BRCA2 mutation. One novel truncating mutation was found in BRCA1 (c.1747A>T) and two in BRCA2 (c.3939delC and c.5763dupT). The 35 identified BRCA1 mutations comprised 13 different alterations. Three recurrent mutations accounted for 71.4% of unrelated individuals with detected gene alterations. The BRCA1 c.5266dupC (5382insC) was detected in 51.4% of mutation positive women. The mutations c.3700_3704del5 and c.181T>G (300T>G) contributed to 11.4% and 8.6% of pathogenic mutations, respectively. A total of eight different mutations were identified in BRCA2. The novel c.5763dupT mutation, which appeared in two unrelated families, was the only recurrent alteration of the BRCA2 gene identified in this study.ConclusionMutational analysis of BRCA1/2 genes in 151 high-risk patients characterized the spectrum of gene alterations and demonstrated the dominant role of the BRCA1 c.5266dupC allele in hereditary breast and ovarian cancer.

Clinicopathologic features and long-term outcome of patients with medullary breast carcinoma managed with breast-conserving therapy (BCT)

The purpose of this study is to compare the clinical characteristics and outcome of medullary carcinoma to infiltrating ductal carcinoma of the breast in a large cohort of conservatively managed patients with long-term follow-up. Chart records of patients with invasive breast cancer managed with breast-conserving therapy (BCT) at the therapeutic radiology facilities of Yale University School of Medicine before 2001 were reviewed. Forty-six cases (1971-2001) were identified with medullary histology; 1,444 patients with infiltrating ductal carcinoma served as a control group. The medullary cohort presented at a younger age with a higher percentage of patients in the 35 years or younger age group (26.1% vs. 6.6%, p < 0.00001). Twelve patients with medullary histology underwent genetic screening, and 6 patients were identified with deleterious mutations. This group showed greater association with BRCA1/2 mutations compared with screened patients in the control group (50.0% vs. 15.8%, p = 0.0035). The medullary cohort was also significantly associated with greater T stage and tumor size (37.0% vs. 17.2% T2, mean size 3.2 vs. 2.5 cm, p = 0.00097) as well as negative ER (84.9% vs. 37.6%, p < 0.00001) and PR (87.5% vs. 48.1%, p = 0.00001) status. As of February 2003, median follow-up times for the medullary and control groups were 13.9 and 14.0 years, respectively. Although breast relapse-free rates were not significantly different (76.7% vs. 85.2%), 10-year distant relapse-free survival in the medullary cohort was significantly better than in the control group (94.9% vs. 77.5%, p = 0.028). Despite poor clinicopathologic features, patients with medullary histology demonstrate favorable long-term distant relapse-free survival. Local control rates of patients with medullary and infiltrating ductal carcinoma are comparable. These findings suggest that patients diagnosed with medullary carcinoma are appropriate candidates for BCT and are associated with favorable long-term prognosis.

Outcome after breast-conserving therapy for patients with stage I or II mucinous, medullary, or tubular breast carcinoma

Outcome after breast-conserving therapy for patients with stage I or II mucinous, medullary, or tubular breast carcinoma

Outcome after breast-conserving therapy for patients with stage I or II mucinous, medullary, or tubular breast carcinoma

Outcome after breast-conserving therapy for patients with stage I or II mucinous, medullary, or tubular breast carcinoma

Medullary breast carcinoma: Outcomes and prognosis with the utilization of chemotherapy

671 Background: Medullary carcinoma of the breast is an uncommon histological type consisting of poorly differentiated cells surrounded by a prominent lymphoid stroma. It is also suggested that these lesions have good prognosis and therefore may not benefit from systemic therapy. We therefore report on our experience with this tumor type. Methods: 143 evaluable patients treated between 1980–2003 at UTMDACC were retrospectively reviewed on an IRB approved protocol. Pathology was reviewed. Outcomes were analyzed by administration of chemotherapy, use of hormonal therapy, pathologic size, and nodal status. Log-rank statistics were used for overall-, local-regional failure-free, and distant metastasis free- survival. Results: Mean age at diagnosis was 44 years (range 24–84)with a mean follow-up of 9 years (range 0.16- 23.3). 71% of patients recieved chemotherapy (n=102) with 88% having a doxorubicin-based regimen. 72% were ER-. 27 had positive nodes with only 6 patients having 4 or more nodes positive. 5 and 10 yr OS, LRFFS, and DMFS for all patients was 82%/75%, 86%/86%, and 84%/80% respectively. Improvement in 5 and 10 yr OS and DMFS was noted with chemotherapy (86%/79%) vs no chemoherapy (72%/66% P=.08) and ( 81%/81% vs 71%/71% P=.08). No improvement was noted with adjuvant hormonal therapy (n=21)(P=.5). 5 and 10 yr OS rates decreased with increasing tumor size with tumors 1 cm or less having 100%/100% vs tumors 1–3cm having 83%/83%, and tumors 3 cm or larger having 74%/69% values (p=.13). LN- patients likewise had improved 5 and 10 yr OS rates (87%/80% vs 75%/61%)(P=.07). No significant difference in OS, LRFFS, or DMFS was noted after stratification of lymph nodes (1–3 vs 4+). Conclusions: Patients with medullary breast cancer benefited from the use of adjuvant chemotherapy. Limited patient numbers preclude comment on adjuvant hormones. Tumors less than 1 cm were most favorable as were those without nodal metastasis. In our series, patients with + nodes and tumor size greater than 1 cm had prognosis similar to that ascribed to invasive ductal carcinoma NOS and may benefit from systemic regimens. Larger datasets should be examined to further clarify therapy recommendations. No significant financial relationships to disclose.

Medullary breast carcinoma: Outcomes and prognosis with the utilization of chemotherapy

671 Background: Medullary carcinoma of the breast is an uncommon histological type consisting of poorly differentiated cells surrounded by a prominent lymphoid stroma. It is also suggested that the...

Immunoglobulin repertoire of B lymphocytes infiltrating breast medullary carcinoma

Tumor specific peptides recognized by T lymphocytes infiltrating solid tumors, as well as the corresponding T cell receptor (TcR) repertoire usage, have been extensively investigated. By contrast, tumor infiltrating B cells and their immunoglobulin (Ig) repertoire have been studied only in a limited number of tumors. The objective of the present study was to determine, whether DNA sequence analysis of the expressed immunoglobulin variable regions of B cells that infiltrate breast cancer, could be used to reveal a potential specific tumor binding capacity of the antibodies. To answer this question, about 200 expressed Ig heavy (VH) and light chain variable gene (VL) regions were cloned, sequenced and comparatively analysed from a typical medullary beast carcinoma (MBC), where the massive B and plasma cell infiltration correlates with favourable prognosis despite of its high grade. The tumor infiltrating B cell Ig heavy and light chain sequences could be classified into clusters, families and subgroups, based on the identity level to germline, showing a pattern of oligoclonality. Some overrepresented clusters could be determined. In the course of a detailed analysis and search in Blastn database, a number of VH and VL sequences showed more than 99% homology to DNA sequences of Ig VH region, with proved tumor antigen binding capacity. Our data suggest, that potential tumor binder Ig VH and VL sequences might be selected using a detailed immunoglobulin variable region analysis. This new approach might have a benefit for further antibody engineering, as difficulties in search for tumor binders by phage library selection might be reduced and the time for selection shortened.

Outcome after breast-conserving therapy for patients with stage I or II mucinous, medullary, or tubular breast carcinoma

Purpose To evaluate the site of first failure of patients with early-stage tubular, mucinous, and medullary breast carcinoma after breast-conserving therapy and compare their results with those of patients with infiltrating ductal carcinoma (IDC). Methods and materials Twenty clinical Stage I and II patients with mucinous carcinoma, 27 with medullary carcinoma, 28 with tubular carcinoma, and 1055 with IDC were identified. The minimal potential follow-up was 10 years. Results No statistically significant difference ( p = 0.15) was seen in the site of first failure between the four histologic types within the first 10 years after treatment. When the IDC tumors were omitted from the comparison, the failure patterns of the remaining three histologic types were not significantly different ( p = 0.31). In a polychotomous logistic model, histologic type was not significantly associated with the site of first failure (all p >0.17). Local failure was significantly associated with age <50 years ( p = 0.04), positive surgical margins ( p = 0.007), lymphovascular invasion ( p = 0.04), and tumors with an extensive intraductal component ( p <0.001). Regional/distant/opposite breast failure was significantly associated with clinical Stage T2 tumors ( p <0.001), four or more positive lymph nodes ( p = 0.004), and lymphovascular invasion-positive tumors ( p <0.001). Second malignancy or death was significantly associated with age at diagnosis >60 years ( p <0.001) and lymphovascular invasion-positive tumors ( p = 0.03). Conclusion No statistically significant difference was noted in the site of first failure between patients with medullary, mucinous, or tubular carcinoma and patients with IDC. Although not statistically significant, we did note a trend toward a lower long-term rate of disease-free survival in patients with IDC.

Mammary pathology of the genetically engineered mouse

Human breast cancer has been modeled in well over 100 types of genetically engineered mice (GEM). Many of the mutated or overexpressed genes found in human breast cancer also initiate mammary cancer in GEM. The histopathology of GEM models of breast cancer have proved to be unique. Most GEM tumors do not resemble the spontaneous tumors induced by the mouse mammary tumor virus (MMTV) or by carcinogenic agents. The pattern of some GEM tumors closely resembles that seen in some human breast cancers. The most provocative and most thoroughly studied GEM group belongs to the ERBB2 (HER2) signal transduction pathway. GEM bearing ERBB2, various forms of mutated ERBB2 and ERBB2-related genes produce tumors via similar molecular mechanisms, and also have a remarkable morphological resemblance to some forms of human breast cancer. Tumors associated with tumor suppressor genes, such as Brca1 and SV40 Tag (that suppresses expression of Rb and p53) tend to resemble poorly differentiated tumors and, in some cases, medullary carcinoma of the human breast. Many of the GEM develop mammary tumors with characteristic or unique gene-specific 'signature' phenotypes that readily can be identified microscopically. The principle that genotype predicts phenotype can be applied to other GEM and extended to include entire molecular pathways. Studies of tumor kinetics in bi-transgenic mice suggest that some combinations of genes are synergistic while others are inhibitory. Although the majority of breast cancer models have been induced using the MMTV-LTR as a promoter, C3(1), WAP, and BLG promoters frequently have been used. Tumors retain the phenotype characteristic of the oncogene, for the most part, regardless of promoter. In some cases, inserting the transgene behind the native promoter or 'knocking-in' an oncogenic variant at the normal gene locus has also resulted in tumors characteristic of the oncogene. GEM with inactivation of tumor suppressor genes generally die with tumors other than mammary tumors. The mammary tumors that do develop tend to be more poorly differentiated, aneuploid tumors with a wider range of phenotypes. However, when crossed with GEM bearing activated transgenes, the tumors are most likely to resemble the phenotype of the transgene. The tumors in bigenic mice do, however, have more pleomorphic and aneuploid cells. The great majority of mouse mammary tumors are hormone independent. This is in contrast to human breast carcinomas, 50% of which express the receptors for estrogen and progesterone, and are dependent (at least partially) on these hormones for growth. The biology of metastasis is also quite different with mouse carcinomas displaying a hematogeneous spread almost exclusively to the lung and with human carcinomas displaying regional lymph node involvement with preferential systemic spread to the bone, brain and liver.

Clinicopathologic features and long-term outcome of patients with medullary breast carcinoma managed with breast-conserving therapy (BCT)

Purpose/Objective: Medullary carcinoma of the breast has distinct pathologic features with unique biologic and clinical characteristics. There are limited reports assessing long-term outcome in this group managed with BCT. The purpose of this study is to compare the clinical characteristics and outcome of medullary carcinoma to infiltrating ductal carcinoma of the breast in a large cohort of conservatively managed patients with long-term follow-up.

Medullary Breast Carcinoma: Prognostic Implications of P53 Expression

Medullary breast carcinoma (MBC) is a rare pathological type of breast cancer. The rate of p53 protein accumulation is higher in MBC than in common invasive ductal carcinoma. Whether this particular feature of MBC influences the outcome after treatment is unknown. We retrospectively analyzed the characteristics, treatment and outcome of 71 patients with MBC treated between 1981 and 1996. The median age was 51 years (range 27–81) and the median clinical tumor size was 25 mm (range 0-70 mm). Breast-conserving treatment was offered when possible: 55 patients had undergone a tumorectomy and radiotherapy while 16 patients had undergone a mastectomy. p53 protein accumulation was determined by immunohistochemistry on paraffin-embedded tumor specimens from 58/71 samples available for this study. The median follow-up for the 56 survivors was 113 months (range 30–241). The 10-year survival and metastasis-free survival rates were 81% and 81.4%, respectively. The local recurrence rate was 16.4%. The two factors predicting outcome were pathological axillary node involvement in the 60 patients who underwent axillary dissection and adjuvant chemotherapy. p53 accumulation was found in 33/58 patients (57%). p53 status was not predictive of survival nor of distant or local recurrences. We confirm that medullary breast carcinoma has a favorable prognosis despite its aggressive pathological features. p53 protein accumulation, found in the majority of MBCs, was not related to outcome.

Medullary breast carcinoma: prognostic implications of p53 expression.

Medullary breast carcinoma (MBC) is a rare pathological type of breast cancer. The rate of p53 protein accumulation is higher in MBC than in common invasive ductal carcinoma. Whether this particular feature of MBC influences the outcome after treatment is unknown. We retrospectively analyzed the characteristics, treatment and outcome of 71 patients with MBC treated between 1981 and 1996. The median age was 51 years (range 27-81) and the median clinical tumor size was 25 mm (range 0-70 mm). Breast-conserving treatment was offered when possible: 55 patients had undergone a tumorectomy and radiotherapy while 16 patients had undergone a mastectomy. p53 protein accumulation was determined by immunohistochemistry on paraffin-embedded tumor specimens from 58/71 samples available for this study. The median follow-up for the 56 survivors was 113 months (range 30-241). The 10-year survival and metastasis-free survival rates were 81% and 81.4%, respectively. The local recurrence rate was 16.4%. The two factors predicting outcome were pathological axillary node involvement in the 60 patients who underwent axillary dissection and adjuvant chemotherapy. p53 accumulation was found in 33/58 patients (57%). p53 status was not predictive of survival nor of distant or local recurrences. We confirm that medullary breast carcinoma has a favorable prognosis despite its aggressive pathological features. p53 protein accumulation, found in the majority of MBCs, was not related to outcome.

Evaluation of outcome after breast conservation therapy (BCT) in patients with stage I and II tubular, mucinous and medullary breast carcinoma

Evaluation of outcome after breast conservation therapy (BCT) in patients with stage I and II tubular, mucinous and medullary breast carcinoma

Apoptosis, proliferation, and Fas (APO‐1, CD95)/Fas ligand expression in medullary carcinoma of the breast

Apoptosis, proliferation, and Fas (APO‐1, CD95)/Fas ligand expression in medullary carcinoma of the breast