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MR imaging of the ipsilateral breast in women with percutaneously proven breast cancer.

OBJECTIVE: The purpose of this study was to review MR imaging findings in the ipsilateral breast in women with percutaneously proven breast cancer. MATERIALS AND METHODS: Retrospective review was performed of records of 70 consecutive women with percutaneously proven unilateral breast cancer who were considered candidates for breast conservation surgery and who had preoperative MR imaging of the ipsilateral breast. MR images and medical records were reviewed. RESULTS: MR imaging identified mammographically and clinically occult cancer other than the index lesion in the ipsilateral breast in 19 women (27%), including infiltrating cancer in 11 women (16%) and ductal carcinoma in situ in eight women (11%). These additional sites of cancer were in the same quadrant as the index cancer in 14 women (20%), in a different quadrant in three women (4%), and in both the same and different quadrants in two women (3%). Additional sites of cancer were more likely in women with, rather than in those without, a family history of breast cancer (42% vs 14%, p < 0.02) and in women whose index cancer was infiltrating lobular rather than other histologies (55% vs 22%, p < 0.06). In 17 women (24%), MR imaging detected ipsilateral lesions that were benign. Changes due to prior percutaneous biopsy were infrequently observed on MR images and included a clip in 12 women (17%) and a small hematoma in two women (3%). CONCLUSION: MR imaging identified additional sites of ipsilateral cancer in 27% of women with percutaneously proven breast cancer. The yield was highest in women with a family history of breast cancer or infiltrating lobular histology in the index cancer. Change after biopsy was infrequent and did not interfere with the MR imaging interpretation.

Adult↗

[Congenital breast deformity is a serious handicap. An important indication for breast reconstruction with silicone implants].

Severe developmental breast deformities cause deep psychological problems in young women and disturb their social relations. New techniques and traditional breast implants, or the combined expander implants permitting gradual augmentation of a small breast, yield results which afford such young women an opportunity of living normal lives. Of 326 applicants for corrective breast surgery, 26 were found to have developmental breast deformities: thoracic deformity (n = 4), scoliosis (n = 1), Amazon syndrome (unilateral amastia or hypoplasia; n = 5), other breast asymmetries (n = 5), or tubular/tuberous deformity, unilaterally (n = 5) or bilaterally (n = 7) (one patient had both tubular deformity and Amazon syndrome). In the 14-20-year-old age group (n = 11), breast correction took the form of conventional implants in two cases, and combined expander implants in six cases, the corresponding figures in the 21-62-year-old age group (n = 15) being eight and five cases, respectively. Only implants were used in 10 cases, and different combinations of nipple/areolar mammoplasty, mastopexy and reduction in 16 cases. Volume symmetry was good in 24 cases and acceptable in two, and breast shape good in 19 cases, acceptable in five cases, but still asymmetrical in the remaining two cases as the patients declined contralateral ptotic breast correction. Nipple/areolar sensitivity was normal and scars good or acceptable in all cases. One patient developed capsular contraction, and another a mild form of striae. Duration of follow-up is over two years in 22 cases.

Adolescent↗

The significance of breast complaints as correlated with age and breast cancer.

A review is presented of 2,000 consecutive new, patients with breast complaints. Emphasis is placed on the specific complaint as correlated with patient age and the incidence of breast cancer. The initial complaints were a lump (50%), an abnormal mammogram (32%), other complaints (8%), breast pain (6%), and nipple discharge (4%). Follow-up information was available for 1,889 patients. The majority of the patients (68%) were under 50 years of age. Of 831 patients to whom a biopsy was recommended, 720 ultimately had a biopsy and 147 cancers were identified. Sixty-five per cent of the cancers were in women aged 50 years or greater. Of the patients aged 50 years or older, 16.1 per cent had breast cancer, while only 4.0 per cent of the patients less than 50 years and 0.8 per cent of the patients less than 30 years of age had breast cancer. The author concludes that the overwhelming majority of patients (92%) referred to a breast surgery practice do not have malignancy. Thus, primary physicians undoubtedly see even a smaller per cent of breast complaints ultimately result in the diagnosis of breast cancer. There is a need to better inform the public as to the significance of breast complaints and to establish more specific criteria for biopsy, particularly in the young, professional, liability threats not withstanding.

Adult↗

Clinical benign disorders of the breast and carcinoma of the breast.

Among 2,506 women with breast disorders seen in consecutive consultations, 345 had carcinoma. Clinical benign breast disorders occurred 6.3 times as frequently as carcinoma of the breast. The lifetime risk of clinical benign breast disorder was calculated to be more than 50 per cent. Clinical benign breast disorders occurred chiefly in young women and carcinoma occurred chiefly in older women. Thus, clinical benign breast disorders precede carcinoma because of the age at which the disorders occur. The incidence of a previous benign biopsy in women with carcinoma was 10.4 per cent and was estimated to be at least 8.2 per cent in the general population. Only a small number of women with carcinoma had previous benign biopsy. The likelihood of finding carcinoma in those women with a previous benign biopsy was 9.2 per cent and in those without 14.6 per cent. Thirty-one of the 36 patients with carcinoma of the breast with a previous benign biopsy were more than 50 years old and 18 were more than 60 years old. It is concluded that women with clinical benign breast disorders do not have an increased risk of having carcinoma of the breast develop.

Adolescent↗

Development of novel steroid sulfatase inhibitors; II. TZS-8478 potently inhibits the growth of breast tumors in postmenopausal breast cancer model rats.

In postmenopausal breast cancer tissue, steroid sulfatase (STS) activity is high and much estrone sulfate also exists; these facts reveal that estrone sulfate may be involved in the growth of breast cancer as an estrogen source. Steroid sulfatase is an enzyme, which catalyzes hydrolysis from estrone sulfate to estrone, and the development of steroid sulfatase inhibitors is expected as novel therapeutic drugs for postmenopausal breast cancer. We have developed a novel compound 2',4'-dicyanobiphenyl-4-O-sulfamate (TZS-8478), which has potent steroid sulfatase-inhibitory activity and exhibits no estrogenicity in vitro and in vivo. To elucidate its usefulness as a therapeutic drug for postmenopausal breast cancer, we examined the breast cancer cell proliferation- and breast tumor growth-inhibitory activity of TZS-8478 in postmenopausal breast cancer model rats. TZS-8478 dose-dependently suppressed the estrone sulfate-stimulated proliferation of MCF-7 cells. Regarding nitrosomethylurea (NMU)-induced postmenopausal breast cancer models, furthermore, TZS-8478 (0.5 mg/kg per day) markedly inhibited the estrone sulfate-stimulated growth of breast tumors similarly to estrone sulfate-depletion. TZS-8478 completely inhibited steroid sulfatase activity in tumor, uterus and liver, and also markedly lowered plasma concentrations of estrone and estradiol. The above mentioned results suggested that TZS-8478 may be useful as a therapeutic drug for estrogen-dependent postmenopausal breast cancer.

Animals↗

Effect of stromal and epithelial cells derived from normal and tumorous breast tissue on the proliferation of human breast cancer cell lines in co-culture.

Stromal and epithelial components surrounding neoplastic cells are believed to be important in tumor regulation. We have studied the effects of stromal and epithelial cells on the proliferation of a variety of breast-cancer epithelial cell lines. Co-culture experiments were performed in which the 2 cell types were separated by a microporous membrane. Under these conditions, fibroblasts from normal breast tissues inhibited the proliferation of MCF-7 cells, but not that of immortalized normal S2T2 cells. In contrast, fibroblasts from cancerous breast tissues did not influence the proliferation of the 2 cell lines tested. Conditioned media (CM) of breast fibroblasts derived from normal tissues were not able to affect MCF-7 cell growth, suggesting complex paracrine interactions between both cell types. Normal breast epithelial cells (NBEC) have also been tested for their ability to regulate the proliferation of breast-cancer epithelial cell lines. Co-culture experiments demonstrated that NBEC inhibited a variety of breast-cancer cell lines. CM from NBEC induced similar results and the inhibitory effect appeared to be specific for epithelial cells from tumorous breast. Moreover, CM from NBEC and normal fibroblasts were shown to contain more TGF beta 1 and amphiregulin than those of MCF-7 cells. We conclude that both the tissue origin and the target tumor cell's phenotype will determine the extent of proliferative response. More important, the tumor-cell growth inhibition induced by fibroblasts and epithelial cells of normal breast tissue may constitute a tumor-growth-regulatory mechanism.

Actins↗

Expression of glycodelin in human breast and breast cancer.

Glycodelin is a 28 kDa glycoprotein with structural homology to beta-lactoglobulins, particularly expressed in steroid-responsive tissues of the female reproductive tract. We previously found that transfection of glycodelin cDNA into MCF-7 breast cancer cells induces differentiation into organized acinar epithelium and up-regulation of epithelial markers. In this study, we used immunohistochemistry, Northern blotting and reverse transcription-polymerase chain reaction (RT-PCR) analyses to study glycodelin expression in normal and in malignant breast tissues. The results were compared with the expression of estrogen (ER) and progesterone receptors (PR) and p53 tumor suppressor protein. Glycodelin was found in ductal and lobular epithelium of 6/6 normal breast tissues, 27/29 morphologically normal breast tissues from breast cancer patients, 6/6 benign lactating adenomas, 21/35 ductal carcinomas, 9/9 tubular carcinomas, 9/9 mucinous carcinomas, 3/3 mixed ductal/tubular carcinomas and 7/11 lobular carcinomas. In the latter, of particular interest was the presence of glycodelin in paranucleolar vacuoles of carcinoma cells. Northern blot analysis of fresh frozen tissues revealed the normal full length 0.9 kb mRNA of glycodelin in ductal breast carcinoma. Using RT-PCR analysis, glycodelin messenger ribonucleic acid was found in 13/13 ductal and in 3/3 tubular tumor tissues. We also detected a splicing variant lacking exon 4, which includes the nucleotide sequence encoding the potential N-glycosylation site at Asn-85. Our results demonstrate the synthesis of glycodelin in normal breast and breast cancer. In addition, we show that the paranuclear vacuole, characteristically present in lobular breast cancer cells, contains abundant amounts of glycodelin.

Adenoma↗

Association of menstrual and reproductive factors with breast cancer risk: results from the Shanghai Breast Cancer Study.

The incidence of breast cancer among women in Shanghai, a traditionally low-risk population, has increased substantially over the past 20 years. To evaluate the association of menstrual and reproductive factors with breast cancer risk and the influence of these factors on the temporal trend of breast cancer incidence, we analyzed data from the Shanghai Breast Cancer Study, a population-based case-control study of breast cancer recently completed among Chinese women in urban Shanghai. In-person interviews were completed for 1,459 women newly diagnosed with breast cancer between ages 25 and 64 and for 1,556 controls frequency-matched to cases by age. Unconditional logistic regression was employed to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) related to menstrual and reproductive factors. Earlier menarcheal age, nulliparity, and later age at first live birth were associated with increased risk of breast cancer among both pre- and post-menopausal women, while never having breast-fed and later age at menopause were associated with elevated risk only among post-menopausal women. Among controls, 32% of younger women (</=40 years) and 24% of older women (>40 years) reported starting menarche at age of 13 or younger, and this factor contributed to 44% of cases diagnosed among younger women and 26% to 28% of cases in older women. Older age at first live birth or at menopause explained a considerable portion of cases diagnosed in older, but not younger, women. Our study suggests that the changes in menstrual and reproductive patterns among women in Shanghai have contributed to the recent increase in breast cancer incidence, particularly among younger women.

Adult↗

High risk of contralateral breast carcinoma in women with hereditary/familial non-BRCA1/BRCA2 breast carcinoma.

BACKGROUND: The objectives of the current study were to estimate the risk of developing contralateral breast carcinoma (CBC) among women with hereditary/familial non-BRCA1/BRCA2 breast carcinoma and to determine the factors that may predict their risk of CBC. METHODS: The study sample consisted of all families (n = 217 families) that were referred between 1994-2001 to the Clinic of Cancer Genetics at the University Hospital of Umeå for suspected hereditary breast carcinoma. The study included all women in the 217 families who had carcinoma of the breast as their first primary invasive malignancy diagnosed between 1970-2001 in northern Sweden. Exclusion criteria were an estimated lifetime risk < 20%, BRCA1/BRCA2 mutation, noninvasive carcinoma (ductal or lobular carcinoma in situ), and bilateral breast carcinoma. In the final analysis, 204 women were included from 120 families. RESULTS: The cumulative probability of developing CBC among women who had hereditary/familial non-BRCA1/BRCA2 breast carcinoma after 20 years was 27.3% (95% confidence interval, 15.0-37.8) compared with the expected risk (4.9%) among women in northern Sweden who had primary breast carcinoma. A significantly increased risk of CBC was associated with age younger than 50 years at the time of diagnosis of the first primary breast carcinoma (P = 0.006). Adjuvant hormone therapy reduced the risk of CBC (P = 0.036). CONCLUSIONS: Women with hereditary/familial non-BRCA1/BRCA2 breast carcinoma had a high risk of developing CBC. This risk was attenuated further among women who were younger at the time of onset, who had a cumulative probability of developing CBC of nearly 40% after 15 years, which is similar to the estimated risk among BRCA1/BRCA2 mutation carriers. The results of this study emphasized the importance of genetic counseling for these women.

Adult↗

Family history of breast cancer, age and benign breast disease.

A major risk factor for breast cancer is having a first-degree family history of the disease. Benign breast disease (BBD), particularly atypical hyperplasia, is also associated with an increased risk of breast cancer. However, the relationship between family history of breast cancer and BBD is unclear. From 1989 through 1997, 80,995 participants in the Nurses' Health Study II were followed; 16,849 reported a first diagnosis of BBD. Pathology slides were reviewed for 1,465 women who reported having a tissue biopsy, and these were classified as nonproliferative BBD, proliferative BBD without atypia or atypical hyperplasia. Women with a family history of breast cancer were more likely to report a physician diagnosis of BBD [rate ratio (RR) = 1.38, 95% confidence interval (CI) 1.29-1.46]. The magnitude of this association declined with age from RR = 1.96 (95% CI 1.55-2.47) at 25-29 years to RR = 1.20 (95% CI 0.95-1.52) at age 45-50 years. Among women with proliferative disease, those with a family history of breast cancer were almost 3 times as likely to have atypia (prevalence odds ratio = 2.72, 95% CI 1.23-5.89) than those with no family history. In conclusion, women with a family history of breast cancer appear to be at increased risk of being diagnosed with BBD, in particular the high-risk types of BBD associated with a greatly increased risk of breast cancer. This link adds weight to the belief that BBD with atypia is a precursor or marker lesion for breast cancer.

Adult↗

A prospective study of breast size and premenopausal breast cancer incidence.

Studies of the association between breast size, as a proxy for mammary gland mass, and breast cancer risk have given equivocal results. Most have been case-control studies with limited statistical power. We conducted a prospective analysis of the relation between breast size as measured by self-reported bra cup size and breast cancer risk among premenopausal women enrolled in the Nurses' Health Study II. Bra cup size at age 20 was assessed among 89,268 premenopausal women aged 29-47 in 1993. Subsequent incident cases of invasive breast cancer were assessed until 2001. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with a Cox proportional hazards model adjusting for potential confounders and risk factors for breast cancer. During 622,732 person-years of follow-up, 803 premenopausal women were newly diagnosed with invasive breast cancer. For women with a BMI below 25 kg/m2, those with a bra cup size of "D or larger" had a significantly higher incidence of breast cancer than women who reported "A or smaller" (covariate adjusted HR=1.80; 95% CI 1.13-2.88; ptrend=0.01). There was no significant association among women with a BMI of 25 kg/m2 or higher. Stratifying by BMI at age 18 at a cutoff point of 21 kg/m2 gave similar results. Larger bra cup size at a young age is associated with a higher incidence of premenopausal breast cancer, though this association is limited to leaner women.

Adult↗

Histologic types of breast carcinoma in relation to international variation and breast cancer risk factors. WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

Associations between breast cancer risk factors and histologic types of invasive breast carcinoma were studied in 2,728 patients. Lobular and tubular carcinomas occurred with increased relative frequency in most high-risk groups. The proportion of these types increased with age to a maximum at 45-49 years and decreased in the following decade. Significantly increased proportions of lobular and tubular carcinomas were also associated with high-risk countries, prior benign breast biopsy, bilateral breast cancer, concurrent mammary dysplasia, high age at first live birth, never-pregnant patients compared to those with a first live birth before age 20, private pay status, and length of education. Nonsignificant increases were associated with family history of breast cancer, less than 5 live births, less than 25 months total of breast feeding, use of oral contraceptives or IUD, and high occupational class. As a general trend, the higher the overall relative risk, the higher the proportion of lobular and tubular carcinomas. The occurrence of other histologic types also increased with increased breast cancer risk, but to a smaller degree than for lobular/tubular carcinomas. It is suggested that all hormonally related, socio-economic and geographic risk factors exert their effect by selectively increasing number of lobular cells at risk. Family history of breast carcinoma and age over 49 years did not follow the general trend parallel increases in the proportion of lobular/tubular carcinomas and breast cancer risk, and may operate through other mechanisms.

Adult↗

Oestrogen receptors alpha and beta differ in normal human breast and breast carcinomas.

The identification of a second oestrogen receptor, oestrogen receptor (ER) beta, has led to a need to assess the relative importance of the classical ERalpha and ERbeta in human breast and breast carcinomas. ERalpha and ERbeta mRNA was assessed in 61 carcinomas, 8 benign breast lesions, and 30 samples of normal breast using reverse transcriptase (RT)-nested polymerase chain reaction (PCR). Immunohistochemical analysis of ERalpha and ERbeta was performed in 62 carcinomas, the 38 non-malignant breast tissues, and 32 normal breast samples with menstrual cycle data. ERalpha mRNA was detected in 92% of breast cancers, with ERbeta mRNA (wild-type and/or variant form) in 85%; 72% had ERalpha protein, 62% progesterone receptor (PgR), and 32% ERbeta. ERalpha protein had a strong correlation with grade; ERbeta did not, although it was present in three of four grade I carcinomas and in special types. There was no correlation between the presence of ERalpha and ERbeta protein. In non-malignant breast, similar expression of ERalpha and beta was observed, apart from expression of ERbeta in stromal cells and myoepithelium, the latter being confirmed by RT-PCR and western blotting. There were differences in ERalpha in relation to the menstrual cycle but not PgR or ERbeta. The findings indicate a need to understand the role and regulation of ERbeta in normal breast and the reason for its down-regulation in mammary carcinogenesis.

Adult↗

Presence of leptin in breast cell lines and breast tumors.

Leptin is the product of the ob gene, reported to be secreted exclusively from adipocytes and thought to control satiety by providing information to the central nervous system. However, the function of leptin appears to be more complex because multiple studies demonstrate its role in hematopoiesis, reproduction, and immunity. In addition, several nonadipose sources of leptin have been reported. The purpose of this study was to examine several breast cancer cell lines and ductal carcinomas of the breast for expression of leptin messenger RNA (mRNA) and protein. For tumor studies, specimens were preassayed for contaminating adipose tissue. Northern blot analyses demonstrated leptin mRNA in several breast cancer cell lines (MCF-7, T47D, and MDA-MB-231), a normal breast epithelial cell line (MCF10A), and four breast tumors. Leptin protein was identified in T47D breast cancer cells by indirect immunofluorescent staining and in samples of the same breast tumors used for Northern studies by enzyme-linked immunosorbent assays (ELISA). This preliminary study suggests that leptin is expressed in malignant epithelial cells of the breast. Further investigation is needed to determine whether this protein plays a role in breast carcinogenesis.

Adipose Tissue↗

A nested case-control study of mammographic patterns, breast volume, and breast cancer (New York City, NY, United States).

The relations of Wolfe mammographic patterns, quantitative mammographic densities, and mammographically estimated breast size to breast cancer risk were investigated prospectively in a case-control study nested in the New York University Women's Health Study, a cohort of 14,291 women in New York City, NY (United States). The archived mammograms of 197 breast cancer cases who were identified during the first 5.5 years of the study and of 521 individually matched controls from the same cohort were retrieved and classified according to Wolfe parenchymal patterns and mammographic densities by two expert radiologists. Breast size and volume were estimated on the mammogram's cranio-caudal projection. In both premenopausal and postmenopausal subjects, the risk of breast cancer increased progressively with increasing density and percent density area. A significantly increased risk was found also for Wolfe pattern DY in premenopausal women and P2 pattern in postmenopausal subjects. In premenopausal women, mammographically determined breast volume and breast height also were associated positively with breast cancer risk. Although the results of the present study confirmed that mammographic parenchymal patterns and densities were important predictors of breast cancer risk, their practical use in screening seems limited due to the high prevalence of high risk patterns.

Adult↗

A population-based study of contralateral breast cancer following a first primary breast cancer (Washington, United States)

To evaluate predictors of contralateral breast cancer risk, we examined data from a nested case-control study of second primary cancers among a cohort of women in western Washington (United States) diagnosed with breast cancer during 1978 through 1990 and identified through a population-based cancer registry. Cases included all women in the cohort who subsequently developed contralateral breast cancer at least six months after the initial diagnosis, but prior to 1992 (n = 234). Controls were sampled randomly from the cohort, matched to cases on age, stage, and year of initial breast cancer diagnosis. Information on potential risk factors for second primary cancer was obtained through medical record abstractions and physician questionnaires. Women who were postmenopausal due to a bilateral oophorectomy (i.e., a surgical menopause) at initial breast cancer diagnosis had a reduction in contralateral breast cancer risk compared with premenopausal women (matched odds ratio [mOR] = 0.25, 95 percent confidence interval [CI] = 0.09-0.68), whereas no reduction in risk was noted among postmenopausal women who had had a natural menopause (mOR = 0.90, CI = 0.39-2.09). Among postmenopausal women, there was a suggestion of a lower risk associated with relatively high parity (2+). A family history of breast cancer was associated with an increased risk (mOR = 1.96, CI = 1.22-5.15) and varied little by menopausal status. Having an initial tumor with a lobular component (c.f. a ductal histology) was not related strongly to risk (mOR = 1.47, CI = 0.79-2.74). The results of the present and earlier studies argue that we have limited ability to predict the occurrence of a contralateral breast tumor. Better predictors will be required before diagnostic and preventive interventions can be targeted to subgroups of patients with unilateral breast cancer.

Adult↗

The use of technetium-99m methoxyisobutylisonitrile breast scintigraphy to evaluate palpable breast masses.

Thirty-eight female patients (age range: 31-79 years) with breast masses underwent technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) breast scintigraphy in order to assess the value of this technique in the detection of breast carcinomas and in their differentiation from benign breast masses. The results showed that 27 of the 32 cases of breast carcinoma were detected by 99mTc-MIBI breast scintigraphy. In contrast, none of the six benign lesions could be detected by this method. The diagnostic sensitivity, specificity and accuracy were 84%, 100% and 87%, respectively, in the differentiation of malignant and benign breast masses. In conclusion, we consider 99mTc-MIBI breast scintigraphy is useful in distinguishing malignancies from benign breast masses.

Adenocarcinoma↗

Breast self-examination and survival from breast cancer: a prospective follow-up study.

A prospective study was conducted to investigate the possible effect of breast self-examination (BSE) on cause-of-death-specific survival rate of breast cancer patients. Six hundred and four breast cancer patients diagnosed in 1984-1986 in Finland, and applying for breast prostheses, were interviewed about both their BSE practices prior to cancer diagnosis and the actual method of tumor detection. No clear differences were observed in the stage distribution or cause of death-specific five-year survival rates between individuals with different BSE practices. After adjustment for potential confounders in the Cox proportional hazards analysis, no differences in risk of breast cancer death were observed for those who performed BSE monthly as compared to those who practised BSE less frequently or not at all. When the method of detection was taken into account, it turned out that only 34 (7.6 %) of the 448 regular BSE practisers had actually detected their cancers by means of BSE. Furthermore, no survival advantage was associated with detection of breast cancer by means of BSE. Those BSE practisers whose cancer was detected by BSE had a similar or slightly worse prognosis compared to BSE practisers whose cancer had been detected by other means. Our results suggest that BSE practice is not beneficial in terms of breast cancer survival, nor is detection of breast cancer by means of BSE. Conclusive evidence should, however, be obtained from prospective randomized studies of breast cancer mortality.

Adult↗