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Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium.

The contribution of BRCA1 and BRCA2 to inherited breast cancer was assessed by linkage and mutation analysis in 237 families, each with at least four cases of breast cancer, collected by the Breast Cancer Linkage Consortium. Families were included without regard to the occurrence of ovarian or other cancers. Overall, disease was linked to BRCA1 in an estimated 52% of families, to BRCA2 in 32% of families, and to neither gene in 16% (95% confidence interval [CI] 6%-28%), suggesting other predisposition genes. The majority (81%) of the breast-ovarian cancer families were due to BRCA1, with most others (14%) due to BRCA2. Conversely, the majority of families with male and female breast cancer were due to BRCA2 (76%). The largest proportion (67%) of families due to other genes was found in families with four or five cases of female breast cancer only. These estimates were not substantially affected either by changing the assumed penetrance model for BRCA1 or by including or excluding BRCA1 mutation data. Among those families with disease due to BRCA1 that were tested by one of the standard screening methods, mutations were detected in the coding sequence or splice sites in an estimated 63% (95% CI 51%-77%). The estimated sensitivity was identical for direct sequencing and other techniques. The penetrance of BRCA2 was estimated by maximizing the LOD score in BRCA2-mutation families, over all possible penetrance functions. The estimated cumulative risk of breast cancer reached 28% (95% CI 9%-44%) by age 50 years and 84% (95% CI 43%-95%) by age 70 years. The corresponding ovarian cancer risks were 0.4% (95% CI 0%-1%) by age 50 years and 27% (95% CI 0%-47%) by age 70 years. The lifetime risk of breast cancer appears similar to the risk in BRCA1 carriers, but there was some suggestion of a lower risk in BRCA2 carriers <50 years of age.

Adult↗

Vaccination with a mixed vaccine of autogenous and allogeneic breast cancer cells and tumor associated antigens CA15-3, CEA and CA125--results in immune and clinical responses in breast cancer patients.

In breast cancer there is often overexpression of the breast cancer antigen CA15-3, the carcinoembryonic antigen (CEA) and the ovarian cancer antigen CA125, which makes them potential target antigens for immunotherapy. In this study, we used a multi-antigen vaccine, which included the following antigens: autologous breast cancer cells (AUTOC), allogeneic breast cancer MCF-7 cells (ALLOC), and the tumor associated antigens CA15-3, CEA and CA125, plus low doses of granulocyte/macrophage-colony-stimulating factor (GM-CSF) and interleukin 2 (IL-2). Forty-two breast cancer patients received weekly subcutaneous vaccination at the 1st, 2nd, 3rd, 7th, 11th and 15th weeks. Their lymphocyte proliferative responses to AUTOC, ALLOC, CA15-3, CEA and CA125 were tested in lymphocyte blastogenesis assays (LBA) before and after vaccination. The disease stage and serum CA15-3, CEA and CA125 concentrations were also determined pre- and post-vaccination. We found that the vaccine was safe, and the only major side effects were swelling at the site of injection, muscle pain, and weakness or fatigue. The vaccine induced a significant increase in post-vaccination lymphocyte proliferative responses to AUTOC, CA15-3, CEA and CA125 but not ALLOC, compared to pre-vaccination (p < 0.05, p < 0.01, p < 0.05, p < 0.01 and p > 0.05, respectively, a paired t Test). Computed tomography (CT), ultrasound or bone scan showed evidence of disease improvement in 2 (12%) patients after vaccination. Hepatic metastases were reduced in size and number and some actually disappeared one patient. Metastatic disease in the L5 vertebra and the skull decreased in size and some osteolytic sites completely healed in a second patient. In addition, 7 patients (44%) had stable disease and 7 patients (44%) had disease progression. We did not find vaccination significantly reduced serum tumor markers CA15-3, CEA and CA125 of these breast cancer patients. These results suggest that the vaccine mixture of autologous and allogeneic breast cancer cells and tumor associated antigens plus GM-CSF and IL-2 can be administered safely to breast cancer patients and there is evidence for improved immunity and clinical efficacy.

Adult↗

Breast-feeding and family planning: a review of the relationships between breast-feeding and family planning.

A number of interrelated factors must be considered when breast-feeding is introduced as a concern for family planning programs: the number of pregnancies and births experienced, age at each pregnancy and birth, duration of the intervals between conceptions, lactation including duration and type, health and nutritional services available to meet the demands of pregnancy, delivery, and postpartum care. The dietary intake of the mother and her health and disease status have an effect on the duration of breast-feeding, and lactation has an effect on her ovulation and birth spacing. Those at particularly high risk include adolescent girls, older grand-multipara women, and families living in poverty. An historical relationship between the reduction in infant and childhood mortality and the falling off of births can be documented. The straightforward benefits on nutritional status of breast-fed infants, the conjunction with the antibody protection afforded by breast milk, served to reduce infant mortality and indirectly served to reduce birth rates. In addition, the prolongation of postpartum anovulatory cycles in breast-feeding women, coupled with sexual mores that postpone sexual relations while a women is breast-feeding in certain groups, will serve to prolong the interbirth intervals. Populations where breast-feeding is customary have been shown to have fewer births than populations where the women do not breast-fed and where infants are artificially fed.

Age Factors↗

Upregulation of estradiol C16 alpha-hydroxylation in human breast tissue: a potential biomarker of breast cancer risk.

BACKGROUND: The biotransformation of the natural estrogen 17 beta-estradiol (E2) via the C16 alpha-hydroxylation pathway is elevated in patients with breast cancer, in subjects at increased risk for developing breast cancer, and in c-Ha-ras-initiated mouse mammary epithelial cells. PURPOSE: To determine whether differences in the extent of E2 C16 alpha-hydroxylation are related to the risk of developing breast cancer, we examined the extent of biotransformation of E2 via the C16 alpha-hydroxylation pathway in the mammary terminal duct lobular units (TDLUs), epithelial organoids that are a presumptive target site of human breast carcinogenesis, and in nontarget component mammary fat tissue. METHODS: Noninvolved mammary tissue was obtained from four patients undergoing reduction mammoplasty and from four undergoing mastectomy for breast cancer. A radiometric assay that measures 3H2O formation caused by stoichiometric 3H exchange from [C16 alpha-3H]E2 was utilized to compare the relative extent of C16 alpha-hydroxylation in explant cultures of TDLUs and mammary fat. RESULTS: The extent of E2 C16 alpha-hydroxylation was 1.83-fold higher (95% confidence interval [CI] = 1.71-1.97) in the TDLUs from reduction mammoplasty (i.e., "low-risk") patients and 7.96-fold higher (95% CI = 6.38-10.55) in the TDLUs from mastectomy (i.e., "high-risk") patients than in the corresponding values observed in the mammary fat. In the TDLUs obtained from the patients undergoing mastectomy for cancer, the extent of this metabolism was 4.56-fold higher (95% CI = 3.97-5.33) than that observed in TDLUs obtained from reduction mammoplasty patients who did not have cancer. CONCLUSION: The increase in the extent of C16 alpha-hydroxylation of E2 in the epithelial organoids of the human breast, TDLUs in particular, may be an important factor for breast cancer induction. This upregulation may represent an endocrine biomarker for the risk of developing breast cancer. IMPLICATION: A larger prospective study is required to confirm the clinical significance of this endocrine biomarker.

Adolescent↗

Role of breast reconstructive surgery in physical and emotional outcomes among breast cancer survivors.

BACKGROUND: Tissue-sparing approaches to primary treatment and reconstructive options provide improved cosmetic outcomes for women with breast cancer. Earlier research has suggested that conservation or restitution of the breast might mitigate the negative effects of breast cancer on women's sexual well-being. Few studies, however, have compared psychosocial outcomes of women who underwent lumpectomy, mastectomy alone, or mastectomy with reconstruction. To address some of these issues, we examined women's adaptation to surgery in two large cohorts of breast cancer survivors. METHODS: A total of 1957 breast cancer survivors (1-5 years after diagnosis) from two major metropolitan areas were assessed in two waves with the use of a self-report questionnaire that included a number of standardized measures of health-related quality of life, body image, and physical and sexual functioning. All P: values are two-sided. RESULTS: More than one half (57%) of the women underwent lumpectomy, 26% had mastectomy alone, and 17% had mastectomy with reconstruction. As in earlier studies, women in the mastectomy with reconstruction group were younger than those in the lumpectomy or mastectomy-alone groups (mean ages = 50.3, 55.9, and 58.9, respectively; P: =.0001); they were also more likely to have a partner and to be college educated, affluent, and white. Women in both mastectomy groups complained of more physical symptoms related to their surgeries than women in the lumpectomy group. However, the groups did not differ in emotional, social, or role function. Of interest, women in the mastectomy with reconstruction group were most likely to report that breast cancer had had a negative impact on their sex lives (45.4% versus 29.8% for lumpectomy and 41.3% for mastectomy alone; P: =. 0001). CONCLUSIONS: The psychosocial impact of type of primary surgery for breast cancer occurs largely in areas of body image and feelings of attractiveness, with women receiving lumpectomy experiencing the most positive outcome. Beyond the first year after diagnosis, a woman's quality of life is more likely influenced by her age or exposure to adjuvant therapy than by her breast surgery.

Adult↗

Body size and breast cancer risk assessed in women participating in the Breast Cancer Detection Demonstration Project.

In a case-control study that included 2,560 breast cancer cases and 2,679 controls, the authors examined the association between body size and breast cancer with the use of measured height and weight of white US women. The subjects were women aged 26-93 years recruited between 1973 and 1975 for participation in the Breast Cancer Detection Demonstration Project, a nationwide breast cancer screening program. After controlling for the effect of potential confounders, the relative risks of breast cancer across increasing quartiles of height were 1.00, 1.07, 1.15, and 1.27 (p = 0.001, test for trend). The effect of weight independent of height was evaluated using indices of relative weight (e.g., weight/height1.5, weight/height2), and the authors identified excess weight as a risk factor for breast cancer among women who had experienced natural menopause and among women aged 50 years or older at diagnosis. Among women aged 50 years or older, for example, the relative risks of breast cancer for increasing quartiles of weight/height1.5 were 1.00, 1.04, 1.40, and 1.29 (p = 0.0006, test for trend). An inverse association between relative weight and breast cancer risk was suggested for women younger than age 50 years at diagnosis. However, the apparent protective effect of high relative weight was restricted to women with small tumors, suggesting a detection bias.

Adult↗

Early diagnosis, place of diagnosis and persistent differences at 10 years in breast cancer survival. Hospitals and breast clinic cases prognosis.

In the Province of Florence (central Italy), the Center for Cancer Prevention (CSPO) runs a breast clinic for early diagnosis of breast cancer at which women can present as self-referrals or be referred by a general practitioner. About 55% of breast cancers incident in the area were diagnosed at CSPO. This paper evaluates the differences observed in 10-year observed and relative survival between hospitals and breast clinic cases. A population-based data set of 1182 invasive cases diagnosed in the years 1985 and 1986 (Tuscany Cancer Registry) was analyzed. Cox models were used to evaluate the effects of place of diagnosis on observed survival. In comparison to hospital cases, breast clinic cases showed a significantly higher frequency of localized cancer (55% vs 37%) and a better relative survival, persistent at 10 years of follow-up (69% vs 58%). The better survival of breast clinic cases persisted after age adjustment (hospitals cases; RR = 0.71, 95% CI: 0.60-0.84) and after age + diffusion of disease adjustment (RR = 0.79, 95% CI: 0.66-0.93). For regionally diffused cancers, breast clinic cases showed a 10-year survival significantly better than hospital cases. In conclusion, even if some bias (i.e. lead-time and length bias) could affect the comparison, breast clinic cases showed a better survival persistent until 10 years after diagnosis. An earlier stage distribution explained, at least partly, the different prognosis.

Adult↗

Medicare breast surgery fees and treatment received by older women with localized breast cancer.

OBJECTIVE: To determine whether area-level Medicare physician fees for mastectomy and breast conserving surgery were associated with treatment received by Medicare beneficiaries with localized breast cancer and to compare these results with an earlier analysis conducted using small areas (three-digit zip codes) as the unit of observation. DATA SOURCE: Medicare claims and physician survey data for a national sample of elderly (aged 67 or older) Medicare beneficiaries with localized breast cancer treated in 1994 (unweighted n = 1,787). STUDY DESIGN: Multinomial logistic regression analysis was used to estimate a model of treatment received as a function of Medicare fees, controlling for other area economic factors, patient demographic and clinical characteristics, physician experience, and region. PRINCIPAL FINDINGS: In 1994, average Medicare fees (adjusted for the effects of modifiers and procedure mix) for mastectomy (MST) and breast conserving surgery (BCS) were 904 dollars and 305 dollars, respectively. Holding other fees and factors fixed, a 10 percent increase in the BCS fee increased the odds of breast conserving surgery with radiation therapy relative to mastectomy to 1.34 (p = 0.02), while a 10 percent decrease in the MST fee increased the odds of breast conserving surgery with radiation therapy to 1.86 (p < 0.01). CONCLUSIONS: Among older women with localized breast cancer, financial incentives appear to influence the use of mastectomy and breast conserving surgery with radiation therapy. This finding is consistent with the hypothesis that physicians are responsive to financial incentives when the alternative procedures have clinically equivalent outcomes and the patient's clinical condition does not dominate the treatment choice. We also find that the fee effects derived from this analysis of individual data with more precise measurement of both diagnosis and treatment are qualitatively similar to the results of the small-area analysis. This suggests that the earlier study was not severely affected by ecological bias or other data limitations inherent in Medicare claims data.

Aged↗

A case control study on the effectiveness of breast cancer screening by clinical breast examination in Japan.

A case-control study was conducted in Miyagi and Gunma prefectures, Japan, to evaluate the effectiveness of breast cancer screening by clinical breast examination (CBE) alone in reducing breast cancer mortality. Case subjects, who were female and had died of breast cancer, were collected from residential registry files and medical records. Control subjects matched in sex, age and residence were randomly selected from residential registry files. The screening histories during 5 years prior to the cases having been diagnosed as breast cancer were surveyed using the examinee files of the screening facilities. Finally, the data of 93 cases and 375 controls were analyzed. The odds ratio (OR) of breast cancer death for participating in screening at least once during 5 years was 0.93 (95% confidence interval (95% CI) 0.48-1.79). The cases were more symptomatic than the controls when screened. If the participants who had had symptoms in their breasts were classified as not screened, the OR decreased to 0.56 (95% CI 0.27-1.18). The case control study suggests that the current screening modality (CBE) lacks effectiveness (OR = 0.93), although it might be effective for an asymptomatic population (OR = 0.56). The number of cases was small, and a larger case-control study is desirable to define whether CBE is effective or not. However, it is necessary to consider the introduction of mammographic screening to reduce breast cancer mortality in Japan.

Adult↗

Cosmetic outcome of breast-conserving therapy in Chinese patients with early breast cancer.

BACKGROUND: Breast-conserving surgery combined with radiotherapy has emerged as an alternative to mastectomy for women with early breast cancer, and cosmetic outcome has correlated closely with the psychosocial and physical well-being of the patient. Cosmetic outcome assessment after breast-conserving therapy in Chinese patients has so far not been conducted among the clinicians, the patients or their spouses. METHODS: The cosmetic results from breast-conserving therapy were evaluated in a group of 33 patients who had been selected as suitable for undergoing local excision, axillary dissection and postoperative radiation therapy for early stage breast cancer. The success of the procedures was assessed by the patients, the clinicians and the patient's spouse, and their ratings were compared with each other. RESULTS: Eighty per cent of the patients and their spouse were satisfied with the cosmetic outcome. Using McNemar's test, when the groups were evaluated on a case-by-case basis, there was a good level of concordance between the patients and their spouses, and that of the patients and the clinicians. CONCLUSIONS: Evaluation of the cosmetic and psychosocial sequelae of breast cancer patients is essential when new approaches to treatment are introduced; our data suggest that cosmetically successful breast conservation is feasible in a selected group of Chinese women with early breast cancer.

Adolescent↗

Was breast conserving surgery underutilized for early stage breast cancer? Instrumental variables evidence for stage II patients from Iowa.

OBJECTIVE: To estimate the average survival effects of breast conserving surgery plus irradiation relative to mastectomy for marginal stage II breast cancer patients in Iowa from 1989-1994. DATA SOURCES/DATA SETTING: Secondary linked Iowa SEER Cancer Registry--Iowa Hospital Association discharge abstract data for women in Iowa with stage II breast cancer from 1989-1994. STUDY DESIGN: Observational instrumental variables (IV) analysis. DATA COLLECTION/EXTRACTION METHODS: Women with stage II breast cancer from the Iowa SEER Cancer Registry 1989-1994 who received all of their inpatient care in Iowa were linked with their respective hospital discharge abstracts. PRINCIPAL FINDINGS: Breast conserving surgery plus irradiation decreased survival relative to mastectomy for marginal stage II breast cancer patients in Iowa during the early 1990s. In this study marginal patients were those whose surgery choices were affected by differences in area treatment rates and access to radiation facilities. CONCLUSIONS: If marginal patients are representative of patients whose treatment choices would be affected by changes in treatment rates, an increase in the breast conserving surgery plus irradiation rate for stage II early stage breast cancer patients would have decreased survival in Iowa during the early 1990s. Further research with newer data and broader samples is needed to make more current and specific assessments.

Aged↗

Can differences in breast cancer utilities explain disparities in breast cancer care?

BACKGROUND: Black, older, and less affluent women are less likely to receive adjuvant breast cancer therapy than their counterparts. Whereas preference contributes to disparities in other health care scenarios, it is unclear if preference explains differential rates of breast cancer care. OBJECTIVE: To ascertain utilities from women of diverse backgrounds for the different stages of, and treatments for, breast cancer and to determine whether a treatment decision modeled from utilities is associated with socio-demographic characteristics. PARTICIPANTS: A stratified sample (by age and race) of 156 English-speaking women over 25 years old not currently undergoing breast cancer treatment. DESIGN AND MEASUREMENTS: We assessed utilities using standard gamble for 5 breast cancer stages, and time-tradeoff for 3 therapeutic modalities. We incorporated each subject's utilities into a Markov model to determine whether her quality-adjusted life expectancy would be maximized with chemotherapy for a hypothetical, current diagnosis of stage II breast cancer. We used logistic regression to determine whether socio-demographic variables were associated with this optimal strategy. RESULTS: Median utilities for the 8 health states were: stage I disease, 0.91 (interquartile range 0.50 to 1.00); stage II, 0.75 (0.26 to 0.99); stage III, 0.51 (0.25 to 0.94); stage IV (estrogen receptor positive), 0.36 (0 to 0.75); stage IV (estrogen receptor negative), 0.40 (0 to 0.79); chemotherapy 0.50 (0 to 0.92); hormonal therapy 0.58 (0 to 1); and radiation therapy 0.83 (0.10 to 1). Utilities for early stage disease and treatment modalities, but not metastatic disease, varied with socio-demographic characteristics. One hundred and twenty-two of 156 subjects had utilities that maximized quality-adjusted life expectancy given stage II breast cancer with chemotherapy. Age over 50, black race, and low household income were associated with at least 5-fold lower odds of maximizing quality-adjusted life expectancy with chemotherapy, whereas women who were married or had a significant other were 4-fold more likely to maximize quality-adjusted life expectancy with chemotherapy. CONCLUSIONS: Differences in utility for breast cancer health states may partially explain the lower rate of adjuvant therapy for black, older, and less affluent women. Further work must clarify whether these differences result from health preference alone or reflect women's perceptions of sources of disparity, such as access to care, poor communication with providers, limitations in health knowledge or in obtaining social and workplace support during therapy.

Adult↗

Breast milk and breast feeding in very low birthweight infants.

The feeding of 17 babies weighing less than 1500 g was examined retrospectively. 12 babies started breast feeding at a mean weight of 1324 g and 10 of them were fully breast fed by a mean weight of 1600 g. Their weight gains were comparable with bottle-fed babies receiving expressed breast milk. Practical aspects of breast feeding were considered to be: a knowledgeable maternal and nursing attitude, close mother and baby contact, early expression of breast milk, and early suckling. The increased incidence of breast feeding by mothers of both low birthweight and term babies ensures regular supplies of fresh breast milk. Therefore, sterilisation or storage of breast milk there is unnecessary.

Breast Feeding↗

Risk of breast cancer in women with history of benign disease of the breast.

A consecutive series of 791 women who had attended diagnostic breast clinics during 1967-70 and been found to be free of malignant disease were later traced to determine their subsequent incidence of breast cancer. Of the 770 (97%) successfully traced, 22 had developed breast cancer. Based on data from the Welsh Cancer Registry only eight cases of breast cancer had been expected, so that the excess risk for the group was 2.7. The increased risk occurred in all age groups and in women deemed "essentially normal" as well as in those who had had a pathological abnormality. The risk was increased when epithelial hyperplasia was present. No excess mortality from breast cancer was apparent, but follow up was short. More breast symptoms were experienced and more biopsies performed than expected in this group of women. Women with a past history of benign breast disease have a slightly increased risk of breast cancer. Selective screening of these women, however, may be uneconomic and a cause of groundless anxiety.

Adolescent↗

The breast pain clinic: a rational approach to classification and treatment of breast pain.

Three hundred and fifty women complaining of breast pain symptoms of sufficient severity to interfere with their normal lifestyle were reviewed in a special breast pain clinic over a 5 year period. Seventy-two patients (21%) had spontaneous resolution of breast pain and they required reassurance only before discharge. Of the remaining 278 patients, accurate classification of breast pain syndromes was achieved in 89%, the commonest syndrome being cyclical breast pain which accounted for 54% of the women followed up. The remaining womens' breast pain was classified as trigger zone (14%), continuous (8%), Tietze's disease (5%), spinal root (4%), duct ectasia (4%) and psychological depression (2%). In the remaining 25 patients (9%) the breast pain could not be classified. The experience from this clinic is that a majority of women complaining of severe breast pain symptoms can be accurately classified and appropriate therapy instituted.

Breast↗

Three-dimensional shaded-surface rendering of MR images of the breast: technique, applications, and impact on surgical management of breast disease.

Contrast material-enhanced magnetic resonance (MR) imaging is reported to be the most accurate modality for determining the extent of breast cancer before surgery. Three-dimensionally rendered MR images can be used as an adjunct in planning breast surgery. Semiautomated methods are used to isolate the breast tissue within high-resolution MR images and to render the skin with a shaded-surface method. Cut-away views reveal lesions in the interior of the breast. Cut-plane shaded-surface display provides the surgeon with information on the size, extent, and spatial relationships of a breast lesion in a simple, intuitive format. This technique can help the surgeon plan a breast biopsy, lumpectomy, or mastectomy that will maximize local control of breast cancer while minimizing cosmetic damage to the unaffected portions of the breast. In a review of 15 clinical cases, cut-plane shaded-surface rendering aided surgical planning in 10 cases.

Adult↗

Multifocal, multicentric, and contralateral breast cancers: bilateral whole-breast US in the preoperative evaluation of patients.

PURPOSE: To evaluate the efficacy of preoperative bilateral whole-breast ultrasonography (US) in the detection of additional multifocal, multicentric, and contralateral cancers and the effect of US information on therapeutic decisions. MATERIALS AND METHODS: Two hundred one patients who had newly diagnosed breast cancer or who were suspected of having breast cancer underwent US examination of the ipsilateral and contralateral breasts with a 10-, 12-, or 13-MHz transducer. All solid lesions found at US alone were classified according to level of suspicion and were selected for biopsy. The US results were compared with mammographic findings. Sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS: In ipsilateral breasts, US depicted 194 (97%) of 201 foci of invasive cancer and 52 (75%) of 69 foci of ductal carcinoma in situ (DCIS), whereas mammography and physical examination depicted 173 (86%) foci of invasive cancer and 56 (81%) foci of DCIS. In the contralateral breast, US depicted 11 (92%) of 12 foci of invasive cancer and four (57%) of seven foci of DCIS, whereas mammography and physical examination depicted six (50%) foci of invasive cancer and five (71%) foci of DCIS. Overall, US depicted mammographically and clinically unsuspected multifocal or multicentric cancers in 28 patients (14%) and contralateral cancer in eight patients (4%). On the basis of these US findings, therapy was correctly changed in 32 patients (16%). The sensitivity, specificity, and positive and negative predictive values of prospective classification of 77 solid lesions detected at US alone were 100% (36 of 36), 51% (21 of 41), 64% (36 of 56), and 100% (21 of 21), respectively. CONCLUSION: Bilateral whole-breast US complements mammography in the preoperative evaluation of patients with breast cancer.

Adult↗

17beta-hydroxysteroid dehydrogenase 14 affects estradiol levels in breast cancer cells and is a prognostic marker in estrogen receptor-positive breast cancer.

Estrogens have an important role in the progression of breast cancer. The 17beta-hydroxysteroid dehydrogenase (17HSD) family has been identified to be of significance in hormone-dependent tissues. 17HSD1 and 17HSD2 are the main 17HSD enzymes involved in breast cancer investigated this far, but it is possible that other hormone-regulating enzymes have a similar role. 17HSD5 and 17HSD12 are associated with sex steroid metabolism, and 17HSD14 is a newly discovered enzyme that may be involved in the estrogen balance. The mRNA expression of 17HSD5, 17HSD12, and 17HSD14 were analyzed in 131 breast cancer specimens by semiquantitative real-time PCR. The results were compared with recurrence-free survival and breast cancer-specific survival of the patients. The breast cancer cell lines MCF7, SKBR3, and ZR75-1 were transiently transfected with 17HSD14 to investigate any possible effect on estradiol levels. We found that high 17HSD5 was related to significantly higher risk of late relapse in estrogen receptor (ER)-positive patients remaining recurrence-free later than 5 years after diagnosis (P = 0.02). No relation to 17HSD12 expression was found, indicating that 17HSD12 is of minor importance in breast cancer. Patients with ER-positive tumors with high expression levels of 17HSD14 showed a significantly better prognosis about recurrence-free survival (P = 0.008) as well as breast cancer-specific survival (P = 0.01), confirmed by multivariate analysis (P = 0.04). Transfection of 17HSD14 in the human breast cancer cells MCF7 and SKBR3 significantly decreased the levels of estradiol, presenting an effect of high expression levels of the enzyme.

17-Hydroxysteroid Dehydrogenases↗