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Overall clinical breast examination as a factor in delayed diagnosis of breast cancer.

HYPOTHESIS: A standardized description of clinical breast examination (CBE) can predict the risk of delayed diagnosis of breast cancer. DESIGN: Survey of case series. SETTING: Breast surgery referral practice. PATIENTS: Consecutive sample of 371 women with 386 breast cancers of any stage for whom overall characteristics of CBE were recorded at the initial consultation. INTERVENTION: None. MAIN OUTCOME MEASURES: Overall breast "durity" (from Latin duritia, meaning "hardness") was recorded as the inverse of whether rib edges could be felt through breast tissue in the most "dur" (firm or hard) part of the breast, usually the upper outer quadrant adjacent to the areola. "Nodularity" was recorded in this same area by means of an ordinal scale ranging from "surface is smooth" to "coarse nodularity." Delayed diagnosis was tabulated if the patient was told that cancer was not present when there was a sign of cancer on CBE, mammogram, and/or pathology slides. Relative risk of delayed diagnosis was determined within categories of nodularity or durity and within nodularity and durity categories combined. RESULTS: Diagnosis was delayed for 35 (9.1%) of cancers. Delay was least common (2 [2.2%] of 92) for less dur and less nodular breasts (relative risk, 1.0), most common (18 [13.5%] of 133) for less dur and more nodular breasts (relative risk, 6.23; 95% confidence interval, 3.58-10.22), and intermediate for other descriptions (chi(2) = 9.08; P =.03). Neither nodularity alone nor durity alone correlated with delay. CONCLUSIONS: A standardized system to describe CBE will alert physicians to an increased risk of delayed diagnosis of breast cancer (especially for women with less dur and more nodular breasts), help improve interpretation of CBE, and reduce delayed diagnosis of breast cancer.

Biopsy↗

Risk of breast cancer with oral contraceptive use in women with a family history of breast cancer.

CONTEXT: Oral contraceptive (OC) use is weakly associated with breast cancer risk in the general population, but the association among women with a familial predisposition to breast cancer is less clear. OBJECTIVE: To determine whether the association between OC use and risk of breast cancer is influenced by family history of the disease. DESIGN AND SETTING: Historical cohort study of 426 families of breast cancer probands diagnosed between 1944 and 1952 at the Tumor Clinic of the University of Minnesota Hospital. Follow-up data on families were collected by telephone interview between 1991 and 1996. PARTICIPANTS: A total of 394 sisters and daughters of the probands, 3002 granddaughters and nieces, and 2754 women who married into the families. MAIN OUTCOME MEASURE: Relative risk (RR) of breast cancer associated with history of OC use by relationship to proband. RESULTS: After accounting for age and birth cohort, ever having used OCs was associated with significantly increased risk of breast cancer among sisters and daughters of the probands (RR, 3.3; 95% confidence interval [CI], 1.6-6.7), but not among granddaughters and nieces of the probands (RR, 1.2; 95% CI, 0.8-2.0) or among marry-ins (RR, 1.2; 95% CI, 0.8-1.9). Results were essentially unchanged after adjustment for parity, age at first birth, age at menarche, age at menopause, oophorectomy, smoking, and education. The elevated risk among women with a first-degree family history of breast cancer was most evident for OC use during or prior to 1975, when formulations were likely to contain higher dosages of estrogen and progestins (RR, 3.3; 95% CI, 1.5-7.2). A small number of breast cancer cases (n = 2) limited the statistical power to detect risk among women with a first-degree relative with breast cancer and OC use after 1975. CONCLUSIONS: These results suggest that women who have ever used earlier formulations of OCs and who also have a first-degree relative with breast cancer may be at particularly high risk for breast cancer. Further studies of women with a strong family history who have used more recent lower-dosage formulations of OCs are needed to determine how women with a familial predisposition to breast cancer should be advised regarding OC use today. JAMA. 2000;284:1791-1798.

Adult↗

An important role for BRCA1 in breast cancer progression is indicated by its loss in a large proportion of non-familial breast cancers.

The presence of BRCA1 protein was determined immunohistochemically in normal and benign breast biopsies, non-familial breast carcinomas and breast carcinomas from one or more individuals from 8 BRCA1 families. Strikingly, little staining was detected in breast carcinomas from BRCA1 families, regardless of the position or type of mutation, whereas strong immunostaining was observed in 28/28 of non-malignant breast biopsies. Furthermore, BRCA1 staining was reduced in non-familial breast carcinomas, since loss of nuclear BRCA1 staining was evident in 19% of non-familial breast carcinomas whilst a similar proportion (20%) showed absence of either cytoplasmic or nuclear BRCA1 staining. Statistical analysis indicates that breast cancer is characterised by a reduction in levels of nuclear BRCA1 in familial (p < 0.001) and non-familial breast cancer (p = 0.001). In non-familial breast cancer absence of nuclear BRCA1, but not cytoplasmic BRCA1, is more common in high grade breast carcinomas (p = 0.03) and in patients with evidence of lymph node involvement (p = 0.05). Correlation between the absence of BRCA1 protein with high grade is consistent with previous findings of a correlation between mutations in the BRCA1 gene and high grade. Our findings provide new evidence in support of BRCA1 as a tumour suppressor protein in non-familial breast cancer.

Adult↗

Breast-conserving surgery after neoadjuvant anthracycline-based chemotherapy for large breast tumors.

BACKGROUND: Randomized trials comparing neoadjuvant versus adjuvant chemotherapy show that primary chemotherapy allows more frequent breast-preserving surgery even though no survival advantage has been demonstrated. The aim of the current study was to determine the predicting factors and the survival impact of breast conservation in patients with large breast tumors treated with neoadjuvant chemotherapy. METHODS: Between January 1987 and December 2001, 594 patients with invasive T2-3 breast carcinoma who were ineligible for breast-conserving surgery (the mean initial tumor diameter was 49 mm) were treated with 3 or 4 courses of an anthracycline-based primary chemotherapy, surgery, and radiotherapy. Various clinicopathologic factors were tested as possible predicting factors of breast-preserving surgery. Survival analyses were performed to determine the implications of breast-conserving surgery on outcome. RESULTS: After primary chemotherapy, 287 (48%) patients were eligible for breast-conserving surgery and 307 patients underwent a mastectomy. Initial tumor diameter > 5 cm, low histologic grade, lobular histology, and multicentricity were independent predicting factors of breast conservation ineligibility in the multivariate analysis (logistic regression). In the univariate survival analysis, a failure of breast-preserving surgery was associated with a poor outcome. Local disease recurrence-free survival rates were similar in patients treated with lumpectomy and mastectomy. CONCLUSIONS: The results reported in the current study suggested that initial diameter, histologic type and grade, and multicentricity are potential prechemotherapy predicting factors of breast conservation. When carefully selected, patients treated with breast conservation had a risk of local disease recurrence similar to the risk of chest wall disease recurrence after mastectomy.

Adult↗

Lipophilin B: A gene preferentially expressed in breast tissue and upregulated in breast cancer.

Lipophilin B (LPB), which is also known as BU101, is a secretoglobin which exists in vivo as a complex with the mammary-specific protein, mammaglobin A (MGA). The aim of our study was to investigate the expression of LPB in a panel of breast and nonbreast tissues and compare its expression with that of MGA. Using RT-PCR, LPB mRNA was detected in 16/25 (64%) of normal breast specimens, 23/30 (77%) of fibroadenomas, 102/156 (65%) of primary breast cancers and in 8/36 (22%) nonbreast tissues. Levels of expression of LPB mRNA were significantly higher in breast cancers compared to both normal breast tissues (p = 0.02) and nonbreast tissue (p < 0.001). In the primary breast cancers, expression of LPB mRNA was positively correlated with the estrogen receptor (p = 0.045) but inversely related to both tumor grade (p < 0.001) and proliferation rates (p = 0.0345). Compared to MGA, expression of LPB was more sensitive but less specific for breast cancer. Using Western blotting, LPB migrated with an approximate molecular mass of 7-8 kDa, the expected molecular mass of free LPB. Immunohistochemical analysis of breast cancers showed that LPB expression was predominantly confined to the cytoplasm of tumor cells. We conclude that expression of LPB is preferentially but not exclusively restricted to breast tissue. Since LPB was expressed relatively specifically in breast tissue and was significantly upregulated in breast carcinomas, it is a promising candidate biomarker for breast cancer.

Biomarkers, Tumor↗

Mammographic breast density and the Gail model for breast cancer risk prediction in a screening population.

BACKGROUND: Estimating an individual woman's absolute risk for breast cancer is essential for decision making about screening and preventive recommendations. Although the current standard, the Gail model, is well calibrated in populations, it performs poorly for individuals. Mammographic breast density (BD) may improve the predictive accuracy of the Gail model. METHODS: Prospective observational cohort of 81,777 women in the San Francisco Mammography Registry presenting for mammography during 1993 through 2002 who had no prior diagnosis of breast cancer. Breast density was rated by clinical radiologists using the Breast Imaging Reporting and Data System classification (almost entirely fat; scattered fibroglandular densities; heterogeneously dense; extremely dense). Breast cancer cases were identified through linkage to Northern California Surveillance Epidemiology End Results (SEER) program. We compared the predictive accuracy of models with Gail risk, breast density, and the combination. All models were adjusted for age and ethnicity. RESULTS: During 5.1 years of follow-up, 955 women were diagnosed with invasive breast cancer. The Gail model had modest predictive accuracy (concordance index (c-index) 0.67; 95% CI 0.65-0.68). Adding breast density to the model increased the predictive accuracy to 0.68 (95% CI .66-.70, p < 0.01 compared with the Gail model alone). The model containing only breast density adjusted for age and ethnicity had predictive accuracy equivalent to the Gail model (c-index 0.67, 95% CI 0.65-0.68). CONCLUSION: The addition of breast density measured by BI-RADS categories minimally improved the predictive accuracy of the Gail model. A model based on breast density alone adjusted for age and ethnicity was as accurate as the Gail model.

Adult↗

Varying levels of family history of breast cancer in relation to mammographic breast density (United States).

OBJECTIVE: We examined the relationship between breast cancer family history and mammographic breast density. METHODS: Participants included 35,019 postmenopausal women aged >or=40 years enrolled in a population-based mammography screening program. We collected data on the number and type of 1st and 2nd degree female relatives with a history of breast cancer and their ages at diagnosis. We used the Breast Imaging Reporting and Data System breast density categories to identify women with fatty (1 = almost entirely fatty or 2 = scattered fibroglandular tissue) and dense (3 = heterogeneously dense or 4 = extremely dense) breasts. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals for dense (N = 18,111) compared to fatty breasts (N = 16,908). RESULTS: The odds of having dense breasts were 17% greater for women with affected 1st degree relatives than women with no family history. The odds increased with more affected 1st degree relatives [>or=3 vs. none (OR = 1.46; 1.05-2.01)] and among women with >or=1 affected 1st degree relative diagnosed <50 years (OR = 1.22; 1.10-1.34). CONCLUSIONS: Having a family history of breast cancer was more strongly associated with mammographic breast density when the affected relatives were more genetically similar. There may be common, yet undiscovered, genetic elements that affect breast cancer and mammographic breast density.

Adipose Tissue↗

The metabolism of androstenedione and testosterone to C19 metabolites in normal breast, breast carcinoma and benign prostatic hypertrophy tissue.

In previous studies from our laboratory of the metabolism of androstenedione (A) and testosterone (T) in breast adipose and breast carcinoma tissue, the aromatization of these compounds, and their interconversion were demonstrated. The present study describes the conversion of androstenedione and testosterone to C19 metabolites in homogenates of normal breast tissue and breast carcinoma tissue and examines the C19 metabolites in homogenates of benign prostatic hypertrophy (BPH) tissue under similar conditions. Tissue homogenates were incubated for 90 min in Krebs-Ringer bicarbonate buffer (pH 7.4) with ATP (3 mM) and NADPH (2.4 mM) as co-factors. Following extraction with ethyl acetate, the metabolites were separated into neutral and phenolic fractions. Identification of specific products was made by thin layer and paper chromatography and recrystallization procedures. The formation of C19 metabolites was 10-fold greater in prostate than in breast tissue. Androsterone was the major product of androstenedione in both breast and prostate. The other 5 alpha-metabolites of androstenedione identified were dihydrotestosterone (DHT) and epiandrosterone (EPI). The 5 beta-metabolite, etiocholanolone (ET10), was identified in both breast and prostate following incubation with androstenedione. Using testosterone as substrate, dihydrotestosterone was the major product in normal breast and BPH. Etiocholanolone was detected in breast, but not in prostate following incubation with testosterone. Aromatization was demonstrated in all incubations with breast tissue, but not in prostate. The results indicate that androstenedione is actively metabolized by both breast and prostate to 5 alpha reduced metabolites. They also identify the formation of etiocholanolone in both tissues. Aromatization was demonstrated only in breast tissue.

Androstenedione↗

Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study. Hereditary Breast Cancer Clinical Study Group.

BACKGROUND: Women with a mutation in BRCA1 or BRCA2 have a high risk of developing breast cancer and of contralateral cancer after the initial diagnosis of breast cancer. Tamoxifen protects against contralateral breast cancer in the general population, but whether it protects against contralateral breast cancer in BRCA1 or BRCA2 mutation carriers is not known. METHODS: We compared 209 women with bilateral breast cancer and BRCA1 or BRCA2 mutation (bilateral-disease cases), with 384 women with unilateral disease and BRCA1 or BRCA2 mutation (controls) in a matched case-control study. Age and age at diagnosis of breast cancer (range 24-74 years) were much the same in bilateral-disease cases and controls, and both groups had been followed up for the same time for a second primary breast cancer. History of tamoxifen use for first breast cancer was obtained by interview, or by self-administered questionnaire. FINDINGS: The multivariate odds ratio for contralateral breast cancer associated with tamoxifen use was 0.50 (95% CI 0.28-0.89). Tamoxifen protected against contralateral breast cancer for carriers of BRCA1 mutations (odds ratio 0.38, 95% CI 0.19-0.74) and for those with BRCA2 mutations (0.63, 0.20-1.50). In women who used tamoxifen for 2-4 years, the risk of contralateral breast cancer was reduced by 75%. A reduction in risk of contralateral cancer was also seen with oophorectomy (0.42, 0.22-0.83) and with chemotherapy (0-40, 0.26-0.60). INTERPRETATION: Tamoxifen use reduces the risk of contralateral breast cancer in women with pathogenic mutations in the BRCA1 or BRCA2 gene. The protective effect of tamoxifen seems independent of that of oophorectomy.

Adult↗

Breast cancer and abortion: collaborative reanalysis of data from 53 epidemiological studies, including 83?000 women with breast cancer from 16 countries.

BACKGROUND: The Collaborative Group on Hormonal Factors in Breast Cancer has brought together the worldwide epidemiological evidence on the possible relation between breast cancer and previous spontaneous and induced abortions. METHODS: Data on individual women from 53 studies undertaken in 16 countries with liberal abortion laws were checked and analysed centrally. Relative risks of breast cancer--comparing the effects of having had a pregnancy that ended as an abortion with those of never having had that pregnancy--were calculated, stratified by study, age at diagnosis, parity, and age at first birth. Because the extent of under-reporting of past induced abortions might be influenced by whether or not women had been diagnosed with breast cancer, results of the studies--including a total of 44000 women with breast cancer--that used prospective information on abortion (ie, information that had been recorded before the diagnosis of breast cancer) were considered separately from results of the studies--including 39000 women with the disease--that used retrospective information (recorded after the diagnosis of breast cancer). FINDINGS: The overall relative risk of breast cancer, comparing women with a prospective record of having had one or more pregnancies that ended as a spontaneous abortion versus women with no such record, was 0.98 (95% CI 0.92-1.04, p=0.5). The corresponding relative risk for induced abortion was 0.93 (0.89-0.96, p=0.0002). Among women with a prospective record of having had a spontaneous or an induced abortion, the risk of breast cancer did not differ significantly according to the number or timing of either type of abortion. Published results on induced abortion from the few studies with prospectively recorded information that were not available for inclusion here are consistent with these findings. Overall results for induced abortion differed substantially between studies with prospective and those with retrospective information on abortion (test for heterogeneity between relative risks: chi2(1) =33.1, p<0.0001). INTERPRETATION: Pregnancies that end as a spontaneous or induced abortion do not increase a woman's risk of developing breast cancer. Collectively, the studies of breast cancer with retrospective recording of induced abortion yielded misleading results, possibly because women who had developed breast cancer were, on average, more likely than other women to disclose previous induced abortions.

Abortion, Induced↗

Estrogen receptor beta in the breast: role in estrogen responsiveness and development of breast cancer.

Breast cancer is one of the most common forms of cancer observed in women. Endogenous estrogen is thought to play a major role in its development and estrogen receptor blockers are the most important drugs in its treatment. It has long been thought that any conditions or exposures, which enhance estrogenic responses, would result in an increased risk for breast cancer. The discovery of the second estrogen receptor, ERbeta, which can have effects opposite to those of the well-known 'original' estrogen receptor (now called ERalpha) challenges this simplistic view. In order to understand breast cancer one must first understand how the normal breast is maintained. The functions of ERbeta in the breast remain to be defined but from what we have learnt about its activities in in vitro systems, this estrogen receptor may have a protective role in the breast. Studies in human and rodent breasts as well as in human breast cancer biopsies reveal that ERbeta is by far the more abundant of the two ERs. Despite the role of estrogen in proliferation of the breast, neither of the two ERs appears to located in epithelial cells which divide in response to estrogen. In order to define the functions of ERbeta in the normal and malignant breast, we have created mice in which the ERbeta gene has been inactivated. Studies of the breasts of ERbeta knock out mice (BERKO) revealed abnormal epithelial growth, overexpression of Ki67 and severe cystic breast disease as mice age.

Animals↗

Breast density and breast cancer risk factors in a high-risk population.

This study investigates relationships between familial and hormonal risk factors and breast density in women at high risk of developing breast cancer. The subjects are a subset of 102 women from the international breast cancer intervention study (IBIS), for whom a series of repeated measurements of breast density were available. Details of familial and hormonal risk factors for breast cancer were collected at entry and multivariate ordered logistic regression used to identify risk factors for increased breast density. Lower body mass index and nulliparity were associated with high breast density, whereas smoking was associated with lower breast density. It is not yet known whether a reduction in breast density will lead to a corresponding reduction in breast cancer risk, so we propose that changes in breast density be investigated as a potential early indicator of efficacy in chemoprevention trials for breast cancer.

Body Mass Index↗

Clinical significance of 99mTc-MIBI breast imaging in the diagnosis of early breast cancer.

OBJECTIVE: To find an effective, sensitive, specific and noninvasive diagnostic method for cancer. METHODS: 109 masses from 102 patients with breast lesions smaller than 2 cm in diameter were divided into three groups to undergo 99mtechnetium-methoxyisobutylisonitrile (99mTc-MIBI) imaging. The results were compared with their pathology. Twenty cases without breast lesions were selected as a control group. Abnormal density of 99mTc-MIBI in the breast and a threshold level 10% higher than that in the counterpart of the healthy breast was regarded as positive. RESULTS: Of 32 breast cancers, positive imaging appeared in 25. Negative imaging was found in 31 of 38 benign breast lesions. Of 39 nonpalpable breast lesions, five cases were breast cancers and 34 cases benign. Positive MIBI imaging appeared in all of the breast cancers, while in the benign lesions, four were positive and 30 negative. No positive imaging was found in the control group. The diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value of 99mTc-MIBI were 88.4%, 89.2%, 88.0%, 75.0% and 95.3%, respectively. CONCLUSIONS: 99mTc-MIBI imaging had high sensitivity and accuracy in the diagnosis of breast cancer, as well as in the differentiation between benign and malignant breast lesions. It could provide reliable information in confirming the diagnosis in patients with clinically suspected breast cancer.

Adolescent↗

Measurement of retinoids and carotenoids in breast adipose tissue and a comparison of concentrations in breast cancer cases and control subjects.

A case-control study of the associations of retinoids and specific carotenoids with breast cancer using concentrations of these nutrients in breast adipose tissue was conducted among women attending a breast clinic in the Boston area in 1989-1992. Breast adipose tissue was collected during breast biopsy. Cases (n = 46) were women whose biopsies revealed invasive or in situ breast cancer; control subjects (n = 63) were women whose biopsies revealed benign disease. We observed inverse associations between breast adipose concentrations of retinoids and carotenoids and risk of breast cancer, although not all were statistically significant. The multivariate-adjusted odds ratio comparing women above the median value of the control group for retinol with those below or equal to the median was 0.71 (95% CI: 0.26, 1.93; NS); corresponding odds ratios were 0.61 (95% CI: 0.23, 1.64; NS) for retinyl palmitate, 0.30 (95% CI: 0.11, 0.85) for beta-carotene, 0.32 (95% CI: 0.11, 0.94) for lycopene, and 0.68 (95% CI: 0.27, 1.73; NS) for lutein/zeaxanthin. There was a nonsignificant positive correlation (r = 0.23, P = 0.15) between breast adipose tissue concentrations of retinol and dietary intake of preformed vitamin A, including supplements measured by using a food-frequency questionnaire. No correlation was found between breast adipose concentrations of carotenoids and intake of dietary carotenoids. These data suggest that higher breast adipose concentrations of retinoids and some carotenoids may be associated with decreased risk of breast cancer and that further examination of these relations is warranted.

Adipose Tissue↗

Pregnancies, breast-feeding, and breast cancer risk in the International BRCA1/2 Carrier Cohort Study (IBCCS).

BACKGROUND: Multiparity, young age at first childbirth, and breast-feeding are associated with a reduced risk of breast cancer in the general population. The breast cancer predisposition gene, BRCA1, regulates normal cell differentiation. Because mammary gland cells divide and differentiate during pregnancy, reproductive factors may influence breast cancer risk in BRCA1/2 mutation carriers differently than they do in noncarriers. METHODS: We performed a retrospective cohort study of 1601 women in the International BRCA1/2 Carrier Cohort Study cohort, all of whom carried a mutation in BRCA1 or BRCA2. Information on reproductive factors was obtained from a questionnaire. At the time of interview 853 subjects were classified with breast cancer. Data were analyzed by using a weighted cohort approach. All statistical tests were two-sided. RESULTS: There was no statistically significant difference in the risk of breast cancer between parous and nulliparous women. Among parous women, an increasing number of full-term pregnancies was associated with a statistically significant decrease in the risk of breast cancer (Ptrend = .008); risk was reduced by 14% (95% confidence interval [CI] = 6% to 22%) for each additional birth. This association was the same for carriers of mutations in either BRCA1 or BRCA2 and was restricted to women older than 40 years. In BRCA2 mutation carriers, first childbirth at later ages was associated with an increased risk of breast cancer compared with first childbirth before age 20 years (20-24 years, hazard ratio [HR] = 2.33 [95% CI = 0.93 to 5.83]; 25-29 years, HR = 2.68 [95% CI = 1.02 to 7.07]; > or = 30 years, HR = 1.97 [95% CI = 0.67 to 5.81]), whereas in BRCA1 mutation carriers, first childbirth at age 30 years or later was associated with a reduced risk of breast cancer compared with first childbirth before age 20 years (HR = 0.58 [95% CI = 0.36 to 0.94]). Neither history of interrupted pregnancies (induced abortions or miscarriage) nor history of breast-feeding was statistically significantly associated with the risk of breast cancer. CONCLUSIONS: BRCA1 and BRCA2 mutation carriers older than 40 years show a similar reduction in breast cancer risk with increasing parity as non-carriers.

Abortion, Induced↗

Do big breasts disadvantage women with breast cancer?

The present study was undertaken in order to discover whether patients with breast cancer in large breasts experienced a delay in the detection of their cancer due to the bulk of the breast and consequently presented with more advanced tumours compared with women with small breasts. Mastectomy specimens were weighed and their dimensions measured, in particular recording breast mass and breast thickness (anterior-posterior depth). Tumour diameter, the number of involved lymph nodes and the oestrogen and progesterone receptor levels were measured as prognostic indices. Although there was no difference in receptor status of tumours from large and small breasts, on presentation, patients with big breasts had larger tumours and more involved lymph nodes than women with small breasts, whether breast size was assessed by weight or thickness. Women with large breasts may therefore be expected to fare worse than those with small breasts.

Breast↗

The determination of short-term breast volume changes and the rate of synthesis of human milk using computerized breast measurement.

The feasibility of using sequential breast volume measurements as a method of studying short-term rates of milk synthesis in women has been established. We have developed a rapid Computerized Breast Measurement system for the determination of breast volume, based upon the Shape Measurement System. A circle encompassing all the breast tissue is drawn in black face paint on the subject's skin. Six patterns of sixty-four horizontal light stripes are projected onto the breast and chest wall surface. A CCD camera relays video images to a computer, which produces a model of the chest by active triangulation. The volume of the breast and the chest wall segment enclosed by the circle is then calculated. The precision of the method was dependent upon the subject repositioning carefully. The coefficient of variation of replicate measurements was 1.6%. The accuracy of the method was established by comparing the change in breast volume before and after a breast-feed with the amount of milk removed by the infant as determined by test weighing. There was a close relationship between the removal of milk by the infant (x) and the change in breast volume (y), (r = 0.93, n = 73, y = 1.10x - 3.25). The rates of milk synthesis between breast-feeds, for six women determined on one to eight occasions, varied from 11 to 58 ml/h. The results show that the amount of milk available in the breast is not necessarily an important determinant of the amount of milk removed by the infant at a breast-feed.

Breast↗

Expression pattern of a homeotic gene, HOXA5, in normal breast and in breast tumors.

INTRODUCTION: Homeotic (HOX) gene products are now known to be functionally associated with breast cancer biogenesis. Recent evidence has indicated that HOXA5 regulates both p53 and progesterone receptor expression levels in breast cancer cells. In addition, HOXA5 has been shown to interact and regulate the activity of another protein referred to as Twist. As homeotic genes play a pivotal role in development, we sought to decipher the expression pattern in both normal breast tissues and in breast carcinomas. METHODS: RT-PCR and immunohistochemistry were performed, to assay the levels of HOXA5 expression, on a panel of normal breast tissue and its corresponding primary breast tumors. RESULTS AND CONCLUSIONS: We show that HOXA5 expression was maintained at stable levels at different reproductive stages of a woman's life, except during lactation. This evidence indicates that HOXA5 may play a role in maintaining the differentiated state within the breast epithelium. However, nearly 70% of all breast carcinomas had decreased HOXA5 protein levels as compared to normal breast tissues. In addition, we demonstrate that HOXA5 protein expression levels in breast carcinomas inversely co-relates with Epidermal Growth Factor Receptor (EGFR) expression. Furthermore, we found that the survival rate amongst the different low levels of HOXA5 expressing breast tumors was not significant, indicative of an early tumorigenesis process in the absence of innate levels of HOXA5 in normal breast cells.

Breast↗