Polymorphism in CYP17, GSTM1 and the progesterone receptor genes and its relationship with mammographic density

Radiologic breast density is one of the predictive factors for breast cancer and the extent of the density is directly related to postmenopause. However, some patients have dense breasts even during postmenopause. This condition may be explained by the genes that codify for the proteins involved in the biosynthesis, as well as the activity and metabolism of steroid hormones. They are polymorphic, which could explain the variations of individual hormones and, consequently, breast density. The constant need to find markers that may assist in the primary prevention of breast cancer as well as in selecting high risk patients motived this study. We determined the influence of genetic polymorphism of CYP17 (cytochrome P450c17, the gene involved in steroid hormone biosynthesis), GSTM1 (glutathione S-transferase M1, an enzyme involved in estrogen metabolism) and PROGINS (progesterone receptor), for association with high breast density. One hundred and twenty-three postmenopausal patients who were not on hormone therapy and had no clinical or mammographic breast alterations were included in the present study. The results of this study reveal that there was no association between dense breasts and CYP17 or GSTM1. There was a trend, which was not statistically significant (P = 0.084), towards the association between PROGINS polymorphism and dense breasts. However, multivariate logistic regression showed that wild-type PROGINS and mutated CYP17, taken together, resulted in a 4.87 times higher chance of having dense breasts (P = 0.030). In conclusion, in the present study, we were able to identify an association among polymorphisms, involved in estradiol biosyntheses as well as progesterone response, and radiological mammary density.

Polymorphism in CYP17, GSTM1 and the progesterone receptor genes and its relationship with mammographic density.

Radiologic breast density is one of the predictive factors for breast cancer and the extent of the density is directly related to postmenopause. However, some patients have dense breasts even during postmenopause. This condition may be explained by the genes that codify for the proteins involved in the biosynthesis, as well as the activity and metabolism of steroid hormones. They are polymorphic, which could explain the variations of individual hormones and, consequently, breast density. The constant need to find markers that may assist in the primary prevention of breast cancer as well as in selecting high risk patients motived this study. We determined the influence of genetic polymorphism of CYP17 (cytochrome P450c17, the gene involved in steroid hormone biosynthesis), GSTM1 (glutathione S-transferase M1, an enzyme involved in estrogen metabolism) and PROGINS (progesterone receptor), for association with high breast density. One hundred and twenty-three postmenopausal patients who were not on hormone therapy and had no clinical or mammographic breast alterations were included in the present study. The results of this study reveal that there was no association between dense breasts and CYP17 or GSTM1. There was a trend, which was not statistically significant (P = 0.084), towards the association between PROGINS polymorphism and dense breasts. However, multivariate logistic regression showed that wild-type PROGINS and mutated CYP17, taken together, resulted in a 4.87 times higher chance of having dense breasts (P = 0.030). In conclusion, in the present study, we were able to identify an association among polymorphisms, involved in estradiol biosyntheses as well as progesterone response, and radiological mammary density.

Malignant phyllodes tumor in the right breast and invasive lobular carcinoma within fibroadenoma in the other: case report.

CONTEXT: The malignant variety of the phyllodes tumor is rare. The occurrence of invasive lobular carcinoma within fibroadenoma is rare as well. DESIGN: Case report. CASE REPORT: A 58-year-old black female patient was referred to the Mastology unit of the Department of Gynecology, Federal University of São Paulo / Escola Paulista de Medicina, in February 1990, presenting an ulcerated tumor in the right breast with fast growth over the preceding six months. She was a virgin, with meno-pause at the age of 45 years and had not undergone hormone replacement treatment. The physical examination showed, in her right breast, an ulcerated tumor of 20 x 30 cm which was not adher-ent to the muscle level, multilobular and with fibroelastic consistency. The axillary lymph nodes were not palpable. The left breast showed a 2 x 3 cm painless, movable nodule, with well-defined edges, and fibroelastic consistency. We performed left-breast mammography, which showed several nodules with well-defined edges, the largest being 2 x 3 cm and exhibiting rough calcification and grouped microcalcifications within it. The patient underwent a frozen biopsy that showed a malignant variant of the phyllodes tumor in the right breast and fibroadenoma in the left one. After that, we performed a total mastectomy in the right breast and an excision biopsy in the left one. Paraffin study confirmed the frozen biopsy result from the right breast, yet we observed that in the interior of the fibroadenoma that was removed on the left, there was a focal area of invasive lobular carcinoma measuring 0.4 cm. The patient then underwent a modi-fied radical mastectomy with total axillary lymphadenectomy. None of the 21 dissected lymph nodes showed evidence of metastasis. In the follow-up, the patient evolved asymptomatically and with normal physical and laboratory examination results up to July 1997.

How should PCNA be assessed? Total of stained cells or only the most intensely stained ones?

OBJECTIVE: This study aimed to analyse whether a marker of proliferative activity (PCNA) could provide a prognosis of tumor evolution and to determine whether different interpretation criteria could alter the results. METHOD: The presence of PCNA in 59 patients of state II (T2 N0.1 M0) mammary carcinoma was determined. RESULT: Numerical proportions of total and intensely stained cells were established. These data were compared with anatomopathological parameters. A significant association between higher cyclin values and worse histological and nuclear grading was encountered, particularly in patients with a "negative axilla" using the PCNA index. Cyclin values were not significant in relation to any parameters when indices from the intensely stained cells were considered exclusively. CONCLUSION: Higher nuclear (NG3) and histological (HGIII) grading, associated with a high PCNA index (> 50), distinguish high-risk patients, and it is more appropriate considering all the stained cells as representative of PCNA indices, thus reflecting tumor aggressiveness.

Leiomyoma of the breast. A case report.

A rare case of leiomyoma of the breast is reported, with a discussion of the clinical aspects and of the differential diagnosis. Excluding tumors originating from the areolar-papillary complex and the skin, this neoplasm is extremely rare, with only 11 cases reported so far. The histogenesis of the lesion is still controversial.

Fine needle aspiration biopsy in diagnosis and treatment of breast pathology. A review.

Seventy-eight women with breast disease were studied aiming to evaluate the importance of the fine needle aspiration biopsy for its diagnosis and forwarding treatment. Our data showed a high diagnostic accuracy with a low level of false negative results and no false positive. The macroscopic appearance of samples is an important aspect. Clear material prevailed in benign pathology (90%) and the presence of blood was usual in malignant tumors (78.3%).

[Breast cancer in the pregnancy-puerperal cycle]. / Câncer de mama no ciclo grávido-puerperal.

From 1978 to 1988, 611 cases of breast cancer were seen by the Mastology Department of the Beneficência Portuguesa Hospital in São Paulo, Brazil. Thirteen (2.12%) cases were associated to pregnancy, and nine (2.4%) became pregnant after treatment. The patients were submitted to surgery and the authors waited till the end of pregnancy to perform the Rt and/or Qt. Two cases could not be submitted to any kind of treatment. Whenever tests indicated fetal maturity, the option was to perform a caesarean section, and oophorectomy was performed in the most advanced cases. Among patients who became pregnant after treatment, initial cases were predominant and their pregnancies went to term with no problem. The authors compare their results to data found in literature and draw attention to anticonception in mastectomized patients.

[Dermatologic drill biopsy (punch): diagnostic procedures in advanced carcinoma of the breast]. / Pinça de biópsia dermatológica ("punch"): procedimento diagnóstico no carcinoma avançado da mama.

Thirty-seven patients with breast tumors in stage III and IV were selected, and a new method to remove fragments of tissue for anatomopathologic study was used. The "punch" of Keyes was introduced towards the tumor, under strong pressure, with clockwise and counter-clockwise rotational movements. In thirty-eight biopsies, the anatomopathologic study allowed the authors to make a perfect evaluation of the structure, and the diagnosis made was of infiltrating carcinoma of the breast. This method proved to be a quick, safe and simple procedure, free of complications, and it allows for anatomopathologic diagnosis in 100% of the cases.