Mutational analysis of BRCA1 and BRCA2 genes in Mexican breast cancer patients.

Germline mutations in the BRCA1 and BRCA2 genes predispose to breast and ovarian cancer. A variable incidence of mutations has been reported for these genes. The contribution of BRCA1 and BRCA2 mutations to Mexican women with breast and/or ovarian cancer is not known. Because of the increasing prevalence of breast cancer in this population, it is necessary to study the presence of mutations in both genes. We screened BRCA1 and BRCA2 genes in 40 patients: 29 patients with a history of breast and/or ovarian cancer, and 11 patients with early-onset breast cancer (< 40 years), through denaturing high performance liquid chromatography analyses. We found two frameshift mutations in BRCA1 and one missense mutation in each gene. Additionally we found several intronic variants as well as synonymous mutations. We found 5% of deleterious mutations in the BRCA genes. Larger studies are needed to establish the significance and prevalence of BRCA mutations among Mexican women.

A descriptive study of second primary malignancies associated to breast cancer in a mexican Hispanic population.

Breast cancer is the second most frequent tumor in Mexico. Patients diagnosed with this cancer have a higher risk of developing a second malignancy. The objective of our study was to see the frequency, types of second cancers, and its impact on survival, in order to be able to deliver a proper and efficient follow up to these patients, because our patients differ from the population of breast cancer in the rest of the world. Our patients are younger and therefore at higher risk. The clinical records of breast cancer patients treated at the Instituto Nacional de Cancerologia Mexico from 1983 to 1992 were reviewed. In 1370 evaluable patients, 77 (5.6%) developed a second neoplasm, of those, 56 (72.7%) in the contralateral breast and 21 in other sites (27.3%), thyroid was the most frequent followed by ovary and endometrium. Mean age of the patients was 51.5 yr, 45.5 for the other breast and 55.5 for other malignancies (p = 0.01). Median survival for all the group was of 180 mo (3-238). Patients were significantly younger in the contralateral breast group, although all our breast cancer patients are younger. The most frequent second malignancy after the other breast, was thyroid followed by ovary and endometrium with similar survival for both groups.

[Expression of cathepsin D in breast cancer and its clinical and histopathological correlations]. / Expresión de catepsina D en carcinoma mamario y sus correlaciones clínicas e histopatológicas.

BACKGROUND: Cathepsin D is a lysosomal protease which is overexpressed in some cases of breast cancer. Several studies done in tumor cytosol have shown that high levels of cathepsin D are associated with poor prognosis in patients with breast cancer but the results are not conclusive using immunohistochemistry methods to assay cathepsin D. OBJECTIVE: To evaluate if cathepsin D, assayed by a immunohistochemical technique using a polyclonal antibody, can be considered an independent prognostic factor in breast cancer. PATIENTS AND METHODS: Paraffine embedded sections of 68 tumor specimens from breast cancer patients in stages I to IV seen at the Instituto Nacional de Cancerologia during the period from 1985 to 1986. RESULTS: From the 68 patients, 35 (51%) had an intense positive staining for cathepsin D, 19 (28%) han mild staining and 14 (21%) were negative. Ten patients with mild staining had artifacts due to deficiencies in the tissue fixation technique. Cathepsin D expression did not have a prognostic value nor association with other clinical and histopathological prognostic factors well established in breast cancer. CONCLUSION: Cathepsin D determined by immunohistochemistry has no prognostic value in breast cancer.

[Prognostic factors in breast cancer with contralateral supraclavicular or axillary lymphatic metastases]. / Factores pronósticos en cáncer de mama con metástasis a ganglios supraclaviculares o axila contralateral.

OBJECTIVE: To evaluate prognostic factor differences between surviving and decreased breast cancer patients in clinical stage IV with supraclavicular or contralateral axilla metastasis when first seen. METHODS: From the clinical records of 13 years (1975-88) two groups of ten patients each were obtained. Group 1 were women alive and free of disease for more than five years. Group 2 had similar characteristics but had died of the disease. In both groups clinical data were evaluated (age, menstrual status and survival); from slides the histologic factors like tumor size, nodal status, fibrosis percentage, inflammatory infiltrate, nuclear grade and necrosis were evaluated; immunohistochemistry of CD34 for angiogenesis, cathepsin D, p53 antioncogen, c-erb-B2 oncogen, epidermic growth factor, estrogen and progesterone receptors and cellular kinetics were performed; Kaplan Meier survival curves were constructed for the factors showing intergroup differences. RESULTS: The factors associated to the living patients were: low inflammatory infiltrate (p = 0.001), low fibrosis (p = 0.007), lower p53 expression (p = 0.03) and positive estrogen receptor (p = 0.03); other factors were marginally associated: positive progesterone receptor (p = 0.07) and having less than 6 positive lymph nodes (p = 0.07).

Intraoperative touch imprint cytology of sentinel lymph nodes in breast cancer: experience at a tertiary care center in Mexico.

BACKGROUND: Sentinel lymph node (SLN) biopsy in patients with breast cancer has emerged as a conservative and promising procedure. One of the most important issues is the intraoperative evaluation of the SLN with a high degree of accuracy by frozen section and/or imprint cytology. The objective of this study was to test the ability of intraoperative touch imprint cytology (ITIC) to predict metastasis on SLN. METHODS: SLNs were freshly examined, bisected in <0.5 cm or serially sectioned at 2 mm intervals on the long axis. Each surface of the section was touched on the glass slide, and stained. Results of ITIC were compared with permanent sections. Sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), and accuracy (Acc) were calculated. False negatives were reviewed. RESULTS: We analyzed 179 SLN from 110 patients. The comparison between ITIC and final results of the SLN showed 139 (77.6%) true negative imprints, and 28 (15.6%) true positive. There were 12 (6.70%) false negative (FN) imprints which included 6 macrometastases, 3 micrometastases, and 3 isolated tumor cells. Re-screening after the definitive results of false negative imprints showed again 10 negative imprints, one with two groups of cells and one with multiple groups of cells. The overall Se was 70% (73.6% for micro/macrometastases and 82.3% for macrometastases), Sp and PPV were 100% in all cases. NPV was 92.1% overall (93.4% micro/macrometastases and 96% in macrometastases).Global accuracy was 93.3% (94.4% for micro/macrometastases and 96% for in macrometastases). CONCLUSIONS: ITIC is excellent to detect macrometastases, however, it fails to detect micrometastases. False negative imprints for macrometastases are mainly due to sampling error. The immediate availability, low cost, high Sp, PPV, preservation of the lymph node for histopathologic examination, avoiding of a second surgery are the major advantages of intraoperative evaluation of SLN.