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Breast health means more than breast cancer. At least 50% of patients seen at a multidisciplinary breast center have benign conditions. Pain, nipple discharge, and a question of a mass are the usual chief complaints. This article provides contemporary information and management guidelines for the common breast conditions associated with these complaints.
Breast disease in the adolescent female is fortunately uncommon, with most presenting lesions being benign. The type and frequency of breast problems in young women less than 20 years of age are discussed in this paper. There were 634 adolescent females (9-19 years) referred to the Wesley Breast Clinic between January 1990 and December 1999. Of these, 62.6% were aged 18-19 years. The commonest reason for referral was a lump or thickening in the breast (n=554, 87.4%). Six hundred and nineteen females had ultrasound performed, with 59% showing no abnormality. The commonest abnormality in the remainder was probable fibroadenoma (n=162). Twenty-two percent of the females in the study had fine needle aspiration performed; none showed suspicious cytology. Twenty-three females had an excision biopsy following their initial visit. Three of these were found to have benign phyllodes tumour. There were no malignancies detected, although one female had previous DCIS diagnosed elsewhere.
BACKGROUND: Cytologic criteria reported to be helpful in the distinction of proliferative breast disease without atypia (PBD) from nonproliferative breast disease (NPBD) have not been rigorously tested. METHODS: Fifty-one air-dried, Diff-Quik-stained fine-needle aspirates (FNA) of palpable breast lesions with biopsy-proven diagnoses of NPBD (34 cases) or PBD (17 cases) were reviewed. The smears were evaluated for the cellularity, size, and architectural arrangement of the epithelial groups; the presence of single epithelial cells and myoepithelial cells; and nuclear characteristics. RESULTS: The only cytologic feature found to be significantly different between PBD and NPBD was a swirling pattern of epithelial cells. A swirling pattern was noted in 13 of 17 PBD cases (76%) and 12 of 34 NPBD cases (35%) (P = 0.008). CONCLUSIONS: Because there is significant overlap in cytologic features between NPBD and PBD, the distinction between the two entities is difficult in cytologic sampling.
Hybridoma technology has now advanced to the point where hundreds of monoclonal antibodies have been produced and are reported to bind to normal and malignant cell surfaces or intracellular organelles. The original hope for tumor-specific antigens has not materialized, but certain antibodies with rather restricted ranges of binding activities have been identified. This panel discusses the use of such monoclonal antibodies in diagnosis, prognosis, and treatment of human breast disease and breast cancer.
Breast cancer is the leading cause of death in women between the ages of 35 and 54. It is estimated that the specialist in obstetrics and gynecology provides health care for more than half of the female population in the United States and should become familiar with both benign and malignant breast conditions. Confronted with the misconception that the disease appears in women "at risk" only and the estimate that one in every nine women born in the United States will develop breast cancer, adequate education, screening, examination, and documentation are essential in the field of breast disease.
Previous studies have emphasized that genetic susceptibility to breast cancer is rare and is expressed primarily as premenopausal breast cancer, bilateral breast cancer, or both. Proliferative breast disease (PBD) is a significant risk factor for the development of breast cancer and appears to be a precursor lesion. PBD and breast cancer were studied in 103 women from 20 kindreds that were selected for the presence of two first degree relatives with breast cancer and in 31 control women. Physical examination, screening mammography, and four-quadrant fine-needle breast aspirates were performed. Cytologic analysis of breast aspirates revealed PBD in 35% of clinically normal female first degree relatives of breast cancer cases and in 13% of controls. Genetic analysis suggests that genetic susceptibility causes both PBD and breast cancer in these kindreds. This study supports the hypothesis that this susceptibility is responsible for a considerable portion of breast cancer, including unilateral and postmenopausal breast cancer.
Sixty-two cases of invasive breast cancer were identified in a large cohort of women previously treated for biopsy-proven benign breast disease (BBD) at the Breast Unit of CSPO, in Florence, along with a group of 315 controls, strictly matched by age and year of diagnosis. A pathologist reviewed and reclassified all the original BBD slides according to recently proposed criteria (no evidence of epithelial proliferation, epithelial proliferation without or with atypia). Information about potential confounding factors was collected during personal interviews. In comparison to the women with "non-proliferative" BBD, women classified as having "proliferative disease without atypia" showed a weak and non-significant increase in risk (OR 1.3; 95% CI: 0.5-3.5). In contrast, women with "atypical hyperplasia" were at very high risk of developing breast cancer (OR 13.0; 95% CI: 4.1-41.7). When planning mammography screening or other large-scale early-diagnosis programmes for breast cancer in the general female population, follow-up of high-risk subgroups of BBD patients should be considered.
An epidemiologic case-control study of 118 breast cancer patients and 233 controls was conducted to test the hypothesis that hair dyes are related to breast cancer. Matched controls were selected by "random digit dialing," and all epidemiologic data were collected by telephone interviews. No overall association was detected. On a prospective basis, the interaction between hair dye exposure and six variables known to be risk factors for breast cancer then were examined: previous benign breast disease (BBD), "ever" versus "never" pregnant, age at first pregnancy, menopause induced by operation, age at menarche, and education. A statistically significant increased risk of breast cancer was found for women with a history of BBD and exposure to hair dyes as compared to women with BBD but no hair dye exposure: The relative risk (RR) was 4.5, and the 95% confidence intervals (C) were 1.20 and 15.78. A total of 24 women (19 patients and 5 controls) reported a history of BBD and hair dye use. Further analysis revealed a significant association between hair dye use and breast cancer among women 40-49 years of age (RR = 3.33; 95% CI: 1.1 and 10.85) and a highly significant (P = 0.0008) dose-response relationship among women who used hair dyes for changing their natural color as opposed to covering gray hair. The numbers of patients and controls included in this study were small and several hypotheses were tested. Additional epidemiologic studies are needed before firm conclusions can be reached concerning the nature of these associations.
We investigated the relationship between serum levels of retinol, beta-carotene, alpha-carotene, lycopene, alpha-tocopherol, and gamma-tocopherol as well as intakes of retinol, carotene, and vitamin E and the risks of breast cancer and proliferative benign breast disease (BBD) in a case-control study of postmenopausal women in the Boston, MA (United States) area. Serum nutrient data were available for 377 women with newly diagnosed stage I or II breast cancer and 173 women with proliferative BBD. Controls were 403 women who were evaluated at the same institutions but did not require a breast biopsy or whose biopsy revealed nonproliferative BBD. We observed no significant associations between serum levels of these micronutrients and risk of proliferative BBD or breast cancer. The risk of breast cancer was decreased among women in the highest quintile of intake of vitamin E from food sources only (odds ratio [OR] for the highest quintile = 0.4, 95 percent confidence interval [CI] = 0.2-0.9; P, trend across quintiles = 0.02) but less so for total vitamin E intake including supplements (OR = 0.7, CI = 0.4-1.3; P, trend = 0.07).
Cyclin D1 plays a critical role in regulating cell-cycle progression. Gene amplification and protein overexpression of cyclin D1 have been detected in breast cancer but little is known concerning whether these changes occur in normal breast tissue and in breast lesions associated with increased risk of development of invasive breast cancer. We looked for cyclin D1 gene amplification and protein overexpression in 30 cases of benign breast disease (16 epithelial hyperplasias without atypia and 14 atypical ductal hyperplasias) and 18 ductal carcinomas in situ by use of differential PCR and immunohistochemical staining. We compared the resulting frequencies to those in 15 cases of normal breast tissue and 17 invasive ductal carcinomas. We found cyclin D1 gene amplification in 15% of those with normal breast tissue, 19% of those with epithelial hyperplasia without atypia, 27% of those with atypical ductal hyperplasia, 35% of those with ductal carcinoma in situ, and 25% of those with invasive ductal carcinoma; corresponding figures for protein overexpression were 13, 13, 57, 50, and 64%. These results suggest that cyclin D1 amplification and protein overexpression can occur before histologic alterations are seen but that the frequencies of these changes are higher in histologic lesions with cellular atypia (atypical hyperplasia and ductal carcinoma in situ), reaching frequencies similar to those observed in invasive carcinoma.
BACKGROUND: Serum prostate-specific antigen (PSA) can be discovered in patients with breast cancer. We used ultrasensitive methods of PSA detection, successfully developed for early detection of PSA recurrence in prostatic-cancer patients, to study PSA in women with breast cancer and benign breast lesions before and after surgery. MATERIALS AND METHODS: Blood samples of 45 women with suspect breast findings were prospectively analyzed for PSA before and after breast surgery. Supersensitive 2nd and 3rd generation DPC assays were used to measure PSA (clinical detection limit of > 0.1 and > 0.02 ng/mL, respectively) and combined with concentration of serum to improve the clinical detection limit to > 0.025 and > 0.005 ng/mL, respectively. PSA concentrations were correlated with histological findings. RESULTS: The most sensitive detection was required to detect PSA preoperatively in 12 out of 45 patients, 8 (31%) out of 26 breast-cancer patients and 4 (25%) out of 16 patients with benign breast lesions. Postoperatively, 13 out of 45 patients were positive for PSA, 7 (27%) breast-cancer patients and 6 (23%) patients with benign breast lesions. CONCLUSIONS: Cancer patients showed the highest concentrations of PSA measured preoperatively and a decrease after surgery that was however not significant. Women with breast lesions expressed serum PSA in one third of the cases studied. PSA expression in serum does not distinguish benign from malignant breast diseases, but it might be valuable for follow-up to analyze whether recurrent disease can be detected with quantitative ultrasensitive PSA measurement.
AIMS AND BACKGROUND: Screening mammography has been shown to be effective in reducing breast cancer mortality in several randomized clinical trials. One major side effect of screening is the diagnosis of benign breast disease (BBD), which is considered as a nonprogressive lesion, except for a small percentage of lesions considered at high risk. We present data referring to service screening programs active in Italy in 2000 and 2001 and participating in the national survey carried out by the Italian Group for Mammography Screening (GISMa). METHODS: To all centers participating in the GISMa National Survey, we submitted a questionnaire regarding the service screening protocol and main indicators of performance of the local program in the years 2000 and 2001. RESULTS: A total of 657 detected BBD cases, registered by 23 Italian breast cancer screening centers in women 50 to 69 years of age, are included in this study. The BBD detection rate was 2.5 per 1000 at the first screening test and 1.05 per 1000 at repeated tests. The benign/malignant ratio was 0.34 at the first and 0.22 at the repeated test. CONCLUSIONS: Detection of BBD occurred frequently in breast screening programs, and prognostic implications should be further investigated. Women should be individually informed at screening, and with greater detail at the moment of the recall for assessment, of the implications of BBD detection and receive the necessary, also psychological, counseling to avoid the possible harm related to breast cancer screening.
Breast thermography was applied to 372 patients (49 with breast cancer and 323 with benign disease) between June 1984 and May 1985 at this Cancer Center. The thermographic findings obtained were quantitated and subjected to multivariate analysis to establish the diagnostic criteria for breast thermography. The result of diagnosis using the criteria revealed 87.8% as the sensitivity ratio and 67.8% as the specificity ratio. Even nonpalpable breast cancer could be diagnosed correctly. These facts and the noninvasive characteristics of this method indicate its validity as a screening test.
Breast tissue from a forensic autopsy series of 486 women (15 to 98 years of age) was studied radiographically and by histologic sampling. Prevalence of Wolfe P2/Dy parenchymal patterns decreased with age. Radiographic nonvascular microcalcification and histologic presence of marked ductal epithelial hyperplasia and lobular microcalcification increased with age. Both of these histologic parameters of increased risk for breast cancer correlated with the presence of radiographic microcalcification and Wolfe P2/Dy parenchymal pattern. The predictive value of the radiographic parameters for presence of "high-risk" proliferative fibrocystic change increased with age.
Breast ductography is a safe and simple technique to outline the duct system of the breast with contrast medium in patients with nipple discharge. The results of 60 successful ductograms are presented and an assessment of its clinical usefulness is made.
Breast vascularization was measured with an 8-MHz continuous wave Doppler pencil probe. Flow values were low in asymptomatic women and high in patients with severe pain or dysplastic changes. Mild treatment with a plant extract produced only a small decrease in breast vascularization. Treatment with norethisterone acetate showed a dose-dependent decrease in blood flow. A good response was seen with a dosage of 5 mg/d, and a dramatic decrease was seen when 10 mg/d was taken. These results showed a good correlation with the patients' symptoms.
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The malignant potential of solid tumors is related to the ability to invade adjacent tissue and to metastasize. These properties of cancer cells depend on the synthesis of proteolytic enzymes which are able to digest adjacent connective tissue and basement membranes. We hypothesized that all elements of the plasminogen activation system might be overexpressed in malignant human breast tumors, functioning as an essential element in tumor invasion and metastasis. As determined by histopathological methods, the malignant tumors showed statistically significantly higher expression of urokinase plasminogen activator (uPA), type-1 plasminogen activator inhibitor (PAI-1), and especially urokinase plasminogen activator receptor (uPAR) than benign tissues. All those elements were present in higher amounts in the cancer cells than in the cells of benign or normal breast tissues. High exhibition of tissue plasminogen activator (tPA) found in cancer seems to be random and not related to the malignant or benign state, since benign and malignant tumors show overexpression of tissue plasminogen activator with similar frequency. When the tumors express high amounts of uPA, they express a high amount of uPAR in 50% of cases and PAI-1 in 57.3% of cases. When urokinase is expressed in low amount, the receptor is low in 28.6% and inhibitor in 21.4% of malignant breast tumors. This statistically significant consensus, 78.6% in the case of urokinase and its receptor and 78.6% in case of urokinase and its inhibitor, suggests that these activities may be the result of a unique mechanism of control, activated in the last steps of malignant transformation.