[Mutations in the BRCA1 gene in young Spanish women with breast cancer]. / Mutaciones en el gen BRCA1 en mujeres españolas jóvenes con cáncer de mama.

BACKGROUND: Germline mutations in the BRCA1 gene have been associated with familial breast/ovarian cancer. Furthermore, women diagnosed of early-onset breast cancer have a higher probability of being carriers of BRCA1 mutations. Our aim was to know prevalence of BRCA1 mutations in women with breast cancer diagnosed before 40 years. PATIENTS AND METHODS: We analyzed genomic DNA samples of 159 women with early-onset breast cancer. Ten fragments of BRCA1 gene covering the 36% of cases with mutations described in the literature were screened. Analysis involved polymerase chain reaction (PCR), single-strand conformation polymorphisms (SSCP) and direct sequencing. RESULTS: Three germline BRCA1 mutations were identified, one of them not previously described. Two mutations were found in women with familial history of breast cancer. Five additional rare variants and polymorphisms were also detected. CONCLUSIONS: The absence of recurrent mutations or mutations detected in other countries, except for the 185delAG mutation, present in Ashkenazim population, shows the influence of ethnic and geographic origin of population studied, and illustrates the difficulties of establishing DNA-based screening tests for hereditary breast cancer.

Immunological quantitation of nuclear steroid receptors to optimize the biological classification of breast tumors.

We used immunological methods to determine cytosolic and nuclear steroid receptors to evaluate the advantages of nuclear receptor measurement in the selection of breast cancer patients for treatment. Around 75% of tumors showed coincidence between nuclear and cytosolic receptors (+/+ or -/-) for estrogen receptor (ER) and for progesterone receptor (PgR). Only cytosolic receptors were detected in around 20% of tumors. Distributed in the ER/PgR phenotypes according to the nuclear or cytosolic receptors, 64% of tumors remained in the same subgroup, whereas 16% of tumors were classified as hormone dependent according to cytosolic and independent according to nuclear receptors, which could be considered as 'false-positive' results. 6% of tumors would be classified as negative according to cytosolic receptors but positive according to nuclear receptors and would correspond to 'false-negative' results by conventional methods. Cytosolic receptor results may overrate the hormone dependence and cause some 'misclassifications' of patients. This could partially explain the lack of response to therapy in some cases.

Epidermal growth factor in plasma and saliva of patients with active breast cancer and breast cancer patients in follow-up compared with healthy women.

We measure EGF in saliva and plasma from 52 patients with active breast cancer, 22 breast cancer patients in follow-up (non-active) and 33 healthy women. EGF concentrations in saliva were significantly higher in patients with active and non-active breast cancer than healthy women, whereas the opposite results were found in plasma. The highest values of EGF in saliva were found in the local recurrence subgroup.

[Expression of pS2 protein in breast cancer and its relationship with estrogen and progesterone receptors]. / Expresión de la proteína pS2 en el cáncer de mama y su relación con los receptores de estrógenos y progesterona.

BACKGROUND: We studied pS2 protein in breast tumors and its relation with estrogen and progesterone receptors and with anatomopathological characteristics of the tumors. MATERIAL AND METHODS: We measured the pS2 content (by IRMA) and steroid receptors content (by EIA) in 151 breast tumors. Results were compared and correlated with tumoral characteristics. RESULTS: 53% of tumors were pS2+. Among them, 91% were estrogen receptors +.86% of estrogen receptors negative tumors were pS2-. We observed correlation between pS2 and estrogen receptors values (r = 0.56; p < 0.0001) and between pS2 and progesterone receptors values (r = 0.53; p < 0.0001). Distributing the tumors in pS2+ and pS2-, we observed association between pS2+ and estrogen receptors + (chi 2 = 45.6; p < 0.0001) and pS2+ and progesterone receptors + (chi 2 = 43.1; p < 0.0001). However, we found a 18.5% of estrogen receptors + pS2- tumors. We observed a significant difference between GII and GIII tumoral grades (chi 2 = 5.51; p < 0.019), with a majority of pS2+ tumors in GII and pS2- tumors in GIII. CONCLUSIONS: The estrogen receptors in estrogen receptors + ps2- tumors may be non functional. The presence of pS2 protein alternative to that of progesterone receptors may indicate a functional heterogeneity of the estrogen receptors system, which is of interest in evaluating prognosis and response to the hormonal therapy.

Estimation of the epidermal growth factor receptor by the hydroxyapatite method in human breast cancer.

Results of epidermal growth factor (EGF) receptor in human breast tumours show large variations, mainly due to the lack of standardization of the assays. Our EGF receptor values are higher than those reported previously which may be due to the use of the hydroxyapatite to separate bound and non-bound ligand in a radioligand assay. We found EGF receptors in 58% (103/178) of the tumours (EGF receptor levels: 3 to 625 fmol/mg of membrane protein, mean = 33.3, median = 17.4), with a median Kd of 0.642 nmol/l. There was an inverse correlation between EGF receptors and estrogen receptors (r = -0.215, p = 0.00002, Kendall correlation). There was a difference between EGF receptor content in grade II (mean = 16.9) and grade III tumours (mean = 59.3) (p = 0.027), but not between histopathological types and lymph node status. The relevance of EGF receptor largely depends on the reliability of its determination. The standardized EORTC methodology is a reproducible alternative which will expand EGF receptor determination and permit comparability of data between laboratories.

[The estrogen receptor/progesterone receptor quotient as an index of the transcriptional activity of estrogen receptors in breast cancer]. / El cociente receptores de estrógenos/receptores de progesterona como índice de la actividad transcripcional de los receptores de estrógenos en el cáncer de mama.

BACKGROUND: The aim of this study was to determine whether the induction of progesterone receptors (PR) for estrogen receptors (ER) in variable in breast cancer, whether it differs among pre and post menopausal women and whether the ER/PR quotient may be an index of tumoral biology. METHODS: The ER and PR content was determined by enzyme immunoassay in 814 breast tumors and the ER/PR quotient was calculated in the ER+PR+ tumors (n = 395). RESULTS: ER/PR values < 1 were more frequent in premenopausal women (66%) than in post menopausal women (38%). No influence was observed with regard to age. CONCLUSIONS: The highest ER/PR values were found in post menopausal women indicating decreased estrogen receptor transcriptional activity in this subgroup contrary to that found in premenopausal women.

Total and unbound cytosolic estrogen and progesterone receptors in myometrium and fibroid after gonadotropin-releasing hormone agonist treatment.

OBJECTIVE: To study the changes in bound and unbound cytosolic estrogen receptor (ER) and progesterone receptor (PR) in fibroid and myometrium after treatment with gonadotropin-releasing hormone agonists (GnRH-a). DESIGN: Prospective randomized study. SETTING: A tertiary institutional hospital. PATIENTS: Thirty premenopausal women with normal regular menstrual cycles and uterine fibroids. INTERVENTIONS: Patients were randomized to receive buserelin acetate for 3 months (n = 20) or no treatment (n = 10) before hysterectomy. MAIN OUTCOME MEASURES: Bound and unbound ER and PR. RESULTS: In nontreated women, values of unbound ER and PR in fibroid were higher than in myometrium. There were no differences in total receptors. The total and unbound ER in myometrium was higher in treated than in nontreated women. There were no differences in fibroid. CONCLUSIONS: The higher content of unbound hormone receptors in fibroid correlates with an exacerbation of the hormone dependence of this tissue compared with myometrium. The increase of total and unbound ER in myometrium after treatment suggests a higher level of synthesis or a lower level of degradation of receptors in this tissue.