Nonpalpable BI-RADS 4 breast lesions: sonographic findings and pathology correlation.

PURPOSE: We aimed to evaluate ultrasonography (US) findings for Breast Imaging Reporting and Data System (BI-RADS) category 4 lesions using BI-RADS US lexicon and determine the positive and negative predictive values (PPV and NPV) of US with respect to biopsy results. METHODS: Sonograms of 186 BI-RADS 4 nonpalpable breast lesions with a known diagnosis were reviewed retrospectively. The morphologic features of all lesions were described using BI-RADS lexicon and the lesions were subcategorized into 4A, 4B, and 4C on the basis of the physician's level of suspicion. Lesion descriptors and biopsy results were correlated. Pathologic results were compared with US features. PPVs of BI-RADS subcategories 4A, 4B, and 4C were calculated. RESULTS: Of 186 lesions, 38.7% were malignant and 61.2% were benign. PPVs according to subcategories 4A, 4B, and 4C were 19.5%, 41.5%, and 74.3%, respectively. Microlobulated, indistinct, and angular margins, posterior acoustic features, and echo pattern were nonspecific signs for nonpalpable BI-RADS 4 lesions. Typical signs of malignancy were irregular shape (PPV, 66%), spiculated margin (PPV, 80%) and nonparallel orientation (PPV, 58.9%). Typical signs of benign lesions were oval shape (NPV, 77.1%), circumscribed margin (NPV, 67.5%), parallel orientation (NPV, 70%), and abrupt interface (NPV, 67.6%). CONCLUSION: BI-RADS criteria are not sufficient for discriminating between malignant and benign lesions, and biopsy is required. Subcategories 4A, 4B, and 4C are useful in predicting the likelihood of malignancy. However, objective and clear subclassification rules are needed.

Gonadotropin level abnormalities in women with cyclic mastalgia.

OBJECTIVES: Women with cyclic mastalgia seem to be at risk of fibrocystic breast disease and/or breast cancer. We studied the relationships between mastalgia and hormone levels throughout the menstrual cycle. STUDY DESIGN: Ostensibly healthy women were monitored during a sum of 326 cycles. A case-control study compared personal and hormonal variables of 30 women experiencing cyclic mastalgia with those of 77 women without this symptom. RESULTS: Except sleeping times, no significant differences were found in personal variables. Cyclic mastalgia and symptoms of fluid retention were slightly associated. Menses and the luteal phase were significantly longer in cases than in controls. Gonadotropin but not ovarian hormone levels were also significantly higher in cases throughout the cycle. CONCLUSION: Cyclic mastalgia is less related to symptoms of fluid retention or to ovarian hormone levels than to regularly high gonadotropin levels, specific inhibitors might thus be used to alleviate the symptom.

Androgen imbalance in premenopausal women with benign breast disease and breast cancer.

OBJECTIVE: The alteration of steroid hormonal status in premenopausal breast disease (benign and malignant) were investigated by comparing the urinary profile of androgens and corticoids. METHODS: The urinary concentrations of 25 androgens and corticoids were quantitatively determined by a gas chromatographymass spectrometry system in patients with benign breast disease (35 cases, 20-54 years), breast cancer (34, 27-54), and healthy controls of similar age (25, 22-51). RESULTS: In premenopausal patients with breast cancer, a significantly lower rate of excretion of 11-deoxy-17-ketosteroids and their metabolites was found in comparison with normal females. These levels were also inversely associated with benign breast disease. No significant differences were found between the three groups for the concentration of 11-oxy-17-ketosteroids, 17-hydroxy-corticoids and their metabolites. The urinary ratio of adrenal androgen metabolites to cortisol metabolites [(11-DOKS & M)/11-OKS] declined in the order of normal female control (4.04 +/- 0.72; mean +/- SD), breast benign mass (2.29 +/- 0.42) and breast cancer (0.94 +/- 0.27). CONCLUSION: Our data suggest that the hormonal imbalance of androgen deficiency and/or corticoid sufficiency is closely associated with the benign and malignant conditions of premenopausal breast disease and the ratio of (11-DOKS & M)/11-OKS may be an effective discriminant factor of these groups.

Urinary tissue factor levels in patients with breast and colorectal cancer.

Activation of blood coagulation is a common complication of cancer in man and experimental animals. The causes of such activation may be multifactorial, but increased production of tissue factor (TF) by the host mononuclear cells may be involved. TF is not only produced by human monocytes (mTF) and tumour cells, but is also found in urine (uTF), where measurements might be clinically important. Using a highly reproducible (intra-assay CV 2.3 per cent and inter-assay CV 8.1 per cent) one-stage kinetic chromogenic assay (KCA) developed by this group, uTF levels were measured in controls [healthy volunteers (n = 57), patients with renal stones and a normal ESR (n = 30)] and in patients with benign and malignant diseases of the breast (n = 94) and large bowel (n = 62). Each benign disease group was sub-divided into inflammatory and non-inflammatory categories. There were no significant differences between the controls and the benign non-inflammatory groups, so they were unified for further analysis. Malignant groups, irrespective of tumour types, showed significantly higher uTF levels than controls (p < 0.001 for breast and p < 0.01 for large bowel). Similarly, breast and colorectal benign inflammatory groups showed significant increases over controls (p < 0.01 and p < 0.001, respectively). Patients with malignant disease showed uTF activity above the upper quartile range of the normal control group for breast, 77.3 per cent, and large bowel, 73 per cent. uTF levels were related to histological tumour grading and were higher in non-surviving patients. In conclusion, uTF levels are raised in malignant and inflammatory disease compared with controls and patients with non-inflammatory conditions. uTF levels may reflect tumour progression.

The urinary dehydroepiandrosterone, androsterone and etiocholanolone excretion of healthy women and women with benign and malignant breast disease.

The 24-h urinary excretion of dehydroepiandrosterone, androsterone and etiocholanolone was followed in healthy women (n = 50) and in women with benign-fibroadenoma (n = 32), microcysts (n = 32), macrocysts (n = 25) and malignant (n = 35) breast disease aged 35-50 years. The data were analysed in three groups each covering 5 years (35-39, 40-44 and 45-49). A significant decrease in the excretion of etiocholanolone and dehydroepiandrosterone was found in women with benign and malignant breast disease when compared to controls. There was no significant decrease in androsterone excretion in women with benign and malignant breast disease when compared to a control group. A high correlation was found between excretion of etiocholanolone and its precursor dehydroepiandrosterone both in women with benign-fibroadenoma (r = 0.7683) or macrocysts (r = 0.7337) and in women with malignant (r = 0.805) breast disease. Dehydroepiandrosterone and, in particular, etiocholanolone excretions were found to decrease significantly with age in women affected by malignant breast disease.

Stability of ego defenses and endocrine responses in women prior to breast biopsy and ten years later.

Thirty women with breast masses were evaluated psychologically and endocrinologically ten years ago while they were awaiting breast biopsy (3). Eight of these women proved to have benign fibrocystic disease and 22 had breast cancer. A significant (p < 0.05) positive correlation was found between extent of failure of psychological "defenses" and cortisol metabolite excretion rate in these 30 women. On follow-up, 12 women had died (11 with cancer and one who had had benign disease); 7 women were lost to follow-up. Of the remaining 11, one refused to participate, leaving 10 women for follow-up study (7 who had had mastectomy for breast cancer and 3 with benign breast lesions). They were reevaluated using the same assessment techniques as 10 years before. The psychological parameters and cortisol metabolite excretion rates did not show a significant change over the span of ten years. These data support the hypothesis that these psychological parameters and cortisol metabolite excretion rates reflect relatively abiding characteristics and are not as much affected by a "psychosocial threat" as previous research has suggested.

Anovulation and increased androgenic activity as breast cancer risk in women with fibrocystic disease of the breast.

The urine of 26 otherwise healthy women with fibrocystic disease of the breast was assayed by gas chromatography for testosterone and androstanediol (5alpha-androstane-3alpha, 17beta-diol), the major metabolite of dihydrotestosterone. The mean values for both androgens were significantly higher than in 18 normal women in the same age range. Sixteen of the 26 fibrocystic disease patients also had endometrial hyperplasia. Since the endometrial specimen was obtained in the premenstrual period, the presence of hyperplasia proved that the menstrual cycle in over two-thirds of the fibrocystic disease patients was nonovulatory.

PIP: Urine of 26 otherwise healthy women with fibrocystic breast disease (FCD) was assayed by gas chromatography for testosterone (Tes) and androstanediol (Ans), the major metabolite of dihydrotestosterone. The 26 patients under study had been subjected 3-5 months previously to biopsies of breast lumps, diagnosed as FCD. The histological features varied from simple cystic formations with moderate epithelial proliferation in 11 women (Group 1) to pronounced intraductal epithelial hyperplasia accompanied by epithelial cell atypia in 15 women (Group 2). The urinary Tes and Ans difference in FCD patients and controls (18 normal women) was significant at the level of p .01 for both androgens. In controls the mean excretion levels of Tes and Ans were 6.5 and 35 mcg/24 hours, respectively. In FCD patients, the mean Tes and Ans values were 17.4 and 68.5 mcg/24 hours, respectively. Group 2 presented a higher urinary Tes level than patients in Group 1, but the difference was not significant. The Ans level of Group 1 patients was significantly above normal (p .01) and near significantly higher (p .08) than that of the Group 2 patients; whereas the Ans level of Group 2 patients did not differ significantly from the normal value. Endometrial specimens showed that 16/26 FCD patients had endometrial hyperplasia. Since the endometrial specimen was obtained in the premenstrual period (Days 20-22), the presence of hyperplasia proved that the menstrual cycle in over two-thirds of the FCD patients was nonovulatory.

Urinary cholesterol. VII. The significance of the excretion of nonesterified cholesterol in patients with uterine carcinomas.

The urinary excretion of nonesterified cholesterol (NEC) in 170 women with cervical and endometrial carcinomas has been investigated. Control patients (236) included: 1) women with other types of (benign and/or malignant diseases of the pelvic organs; 2) patients with non-steroid-related neoplasms; 3) patients with benign and/or malignant breast diseases other than carcinoma; and 4) patients with a variety of non-neoplastic diseases. NEC was determined by a gas-liquid chromatographic procedure. The range of NEC excretion for clinically healthy normal women (64) was previously established by this method. NEC hyperexcretion was defined as any NEC value over 1.5 mg/24 hours. The results showed NEC hyperexcretion in 65 of 68 women with active carcinoma of the cervix, including 13 patients with carcinoma in situ, and in 42 of 45 women with active carcinoma of the endometrium. In contrast, a normal excretion of NEC occurred in all the patients (77) of the first and second control groups, in 39 (80%) of the 48 patients of the third control group (high-risk group), and in 101 of the 111 patients of the fourth control group. Sequential studies performed in patients with uterine carcinomas have demonstrated an almost perfect correlation between the NEC excretion and the clinical status of the patient following surgical and/or radiation therapy. Of 57 patients (31 cervix and 26 endometrium) in which the NEC studies were started after treatment was instituted, 53 have normal NEC excretion in the multiple determination performed to date. Presently these patients have no clinical, chemical, or radiologic evidence of cancer. It is concluded that urinary NEC determination can be used as an additional diagnostic biochemical test to detect active carcinoma of the steroid-producing glands and their main target organs, and that in women with uterine carcinomas, the test can be used as an objective laboratory method to monitor the course of the disease and the response of the patient to therapy.

The excretion of 17-ketosteroids in patients suffering from mastopathia fibrocystica and mammary carcinomas.

Comparative investigations of the urinary excretion of different 17-ketosteroids in healthy women and patients suffering from mastopathia fibrocystica and/or mammary carcinomas had the following results: 1. A clear age dependency of the excretion of 17 ketosteroids during the regenerative period has been shown in all groups investigated, but it could not be observed during the postmenopausal phase. 2. There are no hints by the excretion values for a remarkable contribution of mammary carcinomas to the hormone metabolism of the host. 3. The excretion values of patients suffering from mastopathia fibrocystica confirm epidemiological results, which consider this from of mastopathia a precancerous one.