Efficiency of palpation in clinical detection of breast cancer.

An annual clinical screening test for breast cancer must be simple, brief and efficient. The traditional physical examination of the breast is time-consuming, mainly because of the complicated maneuvers necessary to inspect for retraction. Palpation with the patient supine, however, can be performed quickly. Of 286 primary breast cancers 96% (275) were palpable as a lump, and this was the only clinical sign in 55%. Retraction was the sole clinical sign in only 1%. The combination of retraction and a solid lump is a very specific but not very sensitive test for breast cancer. Retraction in this series was not related to the size of the primary tumour but among the women with a cancerous breast lump was significantly more likely to be found in those over 44 years of age, being present in 52% of these women but only 10% of the younger women. Inspection of the breast can therefore safely be detected from screening breast examinations, whether performed by the physician or the patient.     

The L short-scar mammaplasty: a new approach.

An improved L mammaplasty technique was employed in 178 patients aged 13 to 55 years, with reductions of up to 1280 gm per breast, with small, well-positioned, and undistorted scars. I have obtained a satisfactory final shape of the breast with no major complications over a 3-year follow-up period. The markings are based on chest width and on the quantity of skin that will remain. The technique allows the surgeon to remove more skin, and it is indicated for minor, moderate, and large hypertrophies, as well as for ptotic and asymmetrical breasts. The resection comprises skin and mammary tissue from the inferior and middle portions of the breast, preserving the main lactiferous ducts. In case of hypertrophic breasts, the base is removed, preserving the branches of the lateral cutaneous nerves, which derive from the third, fourth, and fifth intercostal nerves.     

Somatosensory status after pedicled or free TRAM flap surgery: a retrospective study.

The transverse rectus abdominis musculocutaneous (TRAM) flap is widely used in autologous breast reconstructions. In transferring tissue as a pedicled or free flap, alterations in sensibility are unavoidable. This study evaluated somatosensory function in the reconstructed breast at least 2 years after pedicled or free TRAM flap surgery. Thirteen patients who had a pedicled TRAM flap and 13 patients who had a free TRAM flap participated in the study. The patients completed a questionnaire regarding subjective sensibility and their general opinion of the reconstructed breast. Somatosensory examinations to study the sensations of touch, warmth, cold, and pain were performed using nonquantitative and quantitative techniques. An age-matched control group of eight women who had never had breast surgery was also examined because the majority of the women who had breast reconstruction also had a mammaplasty performed on the contralateral breast, which disqualified it as a control. The majority of the patients reported that the reconstructed breast felt like a real breast. However, sensibility to touch, warmth, cold, and pain was decreased in the study groups compared with the control group. No clinically significant differences existed in sensibility between the pedicled and free TRAM flap groups.     

Screening and self examination for breast cancer.

Breast cancer is the major form of cancer in women, with nearly 30,000 new cases and over 15,000 deaths in the United Kingdom each year. Breast screening by mammography has been shown in randomised trials to reduce mortality from breast cancer in women aged 50 and over. An NHS breast screening programme has been in operation in the United Kingdom since 1988. Its aim is to reduce mortality from breast cancer by 25% in the population of women invited to be screened. The uptake of mammography among the eligible population may be the single most important determinant if the programme is to be effective. Primary care teams have an important part to play in encouraging women to attend for screening and in providing information, advice, and reassurance at all stages of the screening process. To date, routine breast self examination has not been shown to be an effective method of screening for breast cancer and should not therefore be promoted as a primary screening procedure. There is, however, a case to be made for women to become more "breast aware."     

Risk of cancer of the breast after legal abortion during first trimester: a Swedish register study.

An increase in induced abortions in Sweden has been accompanied by an increase in the incidence of breast cancer of about 40% in women aged 20-44. To assess whether the apparent risk is real the risk of breast cancer was investigated in practically all Swedish women with a history of a legal abortion in the first trimester before the age of 30 during 1966-74 (n = 49,000). The cohort was followed up in the Swedish cancer register to identify cases of breast cancer diagnosed more than five years after the abortion until the end of 1984. The number of observed cases of breast cancer was 65 compared with an expected number of 84.5, estimated from the contemporary Swedish population with due consideration to age, giving a relative risk of 0.8 (95% confidence interval 0.58 to 0.99). Contrary to most earlier reports, this study did not indicate any overall increased risk of breast cancer after an induced abortion in the first trimester in young women.     

Etiology of breast cancer I. Genetic aspects

The subject of breast cancer is reviewed with particular emphasis on the genetic aspect of its etiology. A number of studies using various approaches gave the same results: the familial form occurs earlier and there is a higher risk in female members of the breast-cancer families. An association between breast cancer and cancer of certain other sites among women is reported. Cytogenetic studies of “cancer families” revealed increased frequency of aneuploidy in some members. However, the role of chromosome abnormalities in carcinogenesis is still not clear.     

Correction of asymmetrical breasts.

An accurate preoperative analysis of the size and contour of asymmetrical breasts allows proper surgical planning and correction. Consideration of the existing defects in each breast and the chest wall, and their relationship to body size, can be combined with the patient's desires for size and contour restoration. Our experience with 14 cases has shown that attention to these principles can give a result that will usually satisfy the patient and the surgeon.     

Lipoprotein alterations, abdominal fat distribution and breast cancer.

Plasma lipid profile and abdominal obesity have been associated with breast cancer risk, however published results have been inconsistent. To clarify these associations we studied lipid and lipoprotein alterations, obesity degree and body fat distribution, in 30 newly diagnosed breast cancer patients without treatment and 30 controls matched by age and menopausal status. Both pre and postmenopausal breast cancer patients presented higher body mass index, waist/hip ratio and insulin levels than their matched controls. An increase in triglycerides and a decrease in HDL-cholesterol, especially in the HDL2 subfraction, were observed in patients with breast cancer. Besides, HDL particle from these patients showed increased apo A1/HDL-cholesterol ratio. These alterations were correlated with waist/hip ratio. The association between lipoprotein alterations and abdominal obesity independent of menopausal status, in untreated newly diagnosed breast cancer patients is reported for the first time in this study.     

Isolation and characterization of a pepsin C zymogen produced by human breast tissues.

An aspartic proteinase present in cyst fluid from women with gross cystic breast disease was purified by a procedure involving affinity chromatography on pepstatin-agarose and size-exclusion high performance liquid chromatography. The amino-terminal sequence of the purified breast proteinase was identical to that corresponding to gastric pepsinogen C. Additional data on cleavage specificity, pH optimum, and immunological properties supported the close relationship between both molecules. Northern blot analysis and polymerase chain reaction amplification studies performed on RNAs obtained from normal and pathological breast tissues demonstrated that the protein is produced by mammary carcinomas and cysts, but not by the normal resting mammary gland. Immunohistochemical staining of paraffin-embedded tissue sections confirmed the existence of a subset of tumors that have the ability to synthesize and secrete this pepsin zymogen. On the basis of these results, we suggest that pepsinogen C expression by human mammary epithelium may be involved in the development of breast diseases, being also of potential interest as a biochemical marker of the hormonal imbalance underlying these pathologies.     

Fine needle aspiration cytodiagnosis of leiomyosarcoma of the breast. A case report

BACKGROUND: Leiomyosarcoma of the breast is a rare tumor. Here we present a case in an elderly female in which the diagnosis was suggested from an aspirate sample. CASE: An 80-year-old female presented with an irregular, firm mass in the left breast of a few months' duration. In view of the clinical suspicion of a tumor, fine needle aspiration was performed. It showed a large number of dissociated cells and compact sheets of spindly and round cells with pleomorphic, hyperchromatic and anaplastic nuclei; mitoses; nucleoli; and somewhat-vacuolated, eosinophilic cytoplasm. Examination of the cell block, tumor tissue and immunostaining further suggested the cytologic impression of a leiomyosarcoma. CONCLUSION: Although leiomyosarcoma of the breast is very rare, fine needle aspiration cytology may allow the diagnosis to be suggested. Correlation with cell block findings and the application of appropriate immunostains as an adjuvant to standard cytologic and histologic stains may allow a more confident diagnosis.     

Immunohistochemical detection of a cross-reacting virus antigen in mouse mammary tumors and human breast carcinomas.

An indirect immunoperoxidase method was first used to localize mouse mammary tumor virus (MMTV) antigens in paraffin sections of mammary tumors of Paris RIII and CD8F1 mice. By using the same method, an antigen with cross-reactivity to a group-specific antigen (gp52, a 52,000 dalton glycoprotein) of MMTV was detected in paraffin sections of human breast carcinomas. The specificity of this reaction with antibody against MMTV was examined by absorption of the IgG with: a) purified gp52; b) several relevant and irrelevant viral preparations; c) normal human plasma, leukocytes, breast tissue, milk, actin, collagen, and hyaluronic acid; d) sheep erythrocytes, bovine mucin and fetal calf serum. Only MMTV and prufied gp52 eliminated the immunohistochemical reaction in human breast tumors. Positive reactions were seen in 73 of 191 (38%) breast carcinomas of various histopathologic types, while negative reactions were obtained in all 137 normal and benign cases tested. A positive reaction of uncertain specificity was observed in foci of apocrine metaplasia. With one exception, 99 carcinomas from 13 organs other than breast and eight cystosarcomas were negative.     

Quantification of cellular properties from external fields and resulting induced velocity: cellular hydrodynamic diameter.

An experimental technique is discussed in which the size distribution of a population of cells is determined by calculating each cell's settling velocity. The settling velocity is determined from microscopically obtained images which were recorded on SVHS tape. These images are then computer imaged and processed, and the cell's location and velocity are determined using a computer algorithm referred to as cell tracking velocimetry (CTV). Experimental data is presented comparing the distribution of human lymphocytes and a human breast cancer cell line, MCF-7, determined using a Coulter counter and the CTV approach.     

Estrogen receptor ligands. Part 13: Dihydrobenzoxathiin SERAMs with an optimized antagonist side chain

An optimized side chain for dihydrobenzoxathiin SERAMs was discovered and attached to four dihydrobenzoxathiin platforms. The novel SERAMs show exceptional estrogen antagonist activity in uterine tissue and an MCF-7 breast cancer cell assay.     

Fine needle aspiration cytology of invasive micropapillary carcinoma of the breast. A case report

BACKGROUND: Invasive micropapillary carcinoma of the breast is uncommon and was characterized only recently. Awareness of this entity and its cytologic appearance is important to allow early diagnosis by fine needle aspiration cytology (FNAC). To our knowledge, only two cases of FNAC of this lesion have been reported in the English-language literature. CASE: An 80-year-old female presented with a firm, nontender mass in the upper outer quadrant of the left breast. FNAC showed ductal carcinoma, and mastectomy showed invasive micropapillary carcinoma. The patient had axillary metastases and received tamoxifen. CONCLUSION: The cytologic features of invasive micropapillary carcinoma are distinctive, with clusters of cells showing hyperchromatic, irregular and crowded nuclei and peripherally located cytoplasm with a rare central lumen. Fibrovascular cores are absent. Although FNAC experience with this lesion is limited, the characteristic cytologic features, including "inside-out" cell clusters, should raise the suspicion of this variant of ductal carcinoma. Differentiation from other papillary lesions and malignancies may be possible, but more experience is needed as the number of reported cases remains limited.     

Metabolism of estrogens in breast cancer.

This extensive literature compilation reviews major studies on estrogen metabolism in cancer, studies which have led to proposed possible etiological roles of estrogens in human breast cancer. Urinary and plasma estrogen excretion patterns and profiles in women with breast cancer are the topics of part 1. Studies of estrogen profiles in women who are at high-risk for breast cancer are critiqued. The estriol hypothesis is presented and criticised in a chapter. The effects of endocrine ablation on urinary estrogen profiles in breast cancer patients are compiled. Production and metabolism of estrogens in women with breast cancer are rendered, including in vivo biotransformation rates and in vitro transformation data. And the search for estrogen metabolites in women with breast cancer is reviewed. In conclusion it is obvious that the question of whether breast cancer patients have an abnormal metabolism of estrogen has not been answered, but further investigations of estrogen metabolism in breast cancer should be continued because: 1) the possibility that estrogens are carcinogenic has not been ruled out; 2) receptors have been discovered which do correlate with hormone dependency of tumors; 3) present evidence suggests that neoplasm may induce abnormal estrogen metabolism; 4) directional changes of estrogen metabolism that occur in pregnancy may also occur in women with target tissue neoplasia; 5) hepatic tissue's relationship to breast cancer has not received attention; and 6) the role of peripheral aromatization in the pathogenesis of mammary cancer is not yet understood.     

Reproductive events and family history as risk factors for breast cancer in northern Alberta.

Reproductive events and family history as risk factors for breast cancer in northern Alberta were investigated with the use of data from a computerized population-based registry. Women aged 30 to 79 years attending diagnostic breast clinics at the Cross Cancer Institute from 1971 through 1975 constituted the two study groups; 1232 women had diagnosed breast cancer (malignant disease group) and 602 women were clinically free of all types of breast disease (control group). An increased relative risk of breast cancer was found in women with a family history of breast cancer, those who gave birth to their first term infant at age 30 years or older, those in whom more than 15 years elapsed between menarche and that birth, and those with a late natural menopause. There was a decreased risk, relative to nulliparity, in the postmenopausal women who first gave birth to a term infant 5 years or less after menarche. Artificial menopause (bilateral oophorectomy), parity and age at menarche had no apparent effect on the risk. The pattern of risk factors in northern Alberta differed from that reported for other geographic areas, including other provinces of Canada, thus emphasizing the need for local studies in the planning of screening programs.     

BRCA1 sequence variations in 160 individuals referred to a breast/ovarian family cancer clinic. Institut Curie Breast Cancer Group.

An account of familial aggregation in breast/ovarian cancer has become possible with the identification of BRCA1 germ-line mutations. We evaluated, for 249 individuals registered with the Institut Curie in Paris, the prior probability that an individual carried a mutation that predisposes to these diseases. We chose 160 women for BRCA1 analysis: 103 with a family history of breast cancer and 57 with a family history of breast-ovarian cancer. To detect small mutations, we generated and analyzed 35 overlapping genomic PCR products that cover the coding portion of the gene, by using denaturing gradient gel electrophoresis. Thirty-eight truncating mutations (32 frameshifts, 4 nonsense mutations, and 2 splice variants) were observed in 15% of women with a family history of breast cancer only and in 40% of those with a history of breast-ovarian cancer. Twelve of 25 distinct truncating mutations identified were novel and unique. Most BRCA1 mutations that had been reported more than five times in the Breast Cancer Information Core were present in our series. One mutation (5149del4) observed in two apparently unrelated families most likely originates from a common ancestor. The position of truncating mutations did not significantly affect the ratio of the risk of breast cancer to that of ovarian cancer. In addition, 15 DNA variants (14 missense mutations and 1 neutral mutation) were identified, 9 of which were novel. Indirect evidence suggests that seven of these mutations are deleterious.     

Heterogeneity analysis of breast cancer families by using age at onset as a covariate.

An extension of the usual mixture model of heterogeneity (two family types, one with and one without linkage) is proposed by introducing age at onset as a covariate. The extended model defines age-dependent penetrances where the exact parametrization of age-at-onset distributions depends on the given genotype and family type (linked or unlinked). This extension was applied to breast cancer families. We postulated that the mean age at onset in individuals affected by the linked gene was lower than the mean age at onset in all other affected individuals. Linkage heterogeneity for breast cancer families was detected at a significance level of .003.     

Breast cancer found at the time of breast reduction.

In a recent study involving 27,500 women who had breast reduction surgery in Ontario, Canada, 17 women who were diagnosed as having breast cancer at the time of their breast reduction surgery were identified. The aims of this study were to (1) describe a population-based series of patients who had breast cancer diagnosed at the time of breast reduction, (2) describe the treatment of these cancers, and (3) compare their survival rate with survival in patients in the general population who had breast cancer. Information about these women, their treatment, and outcome was extracted from hospital records, pathology reports, and reports from regional cancer centers. The chance of finding an invasive breast cancer at the time of breast reduction was 0.06 percent, which is lower than what has been reported previously. Sixty-seven percent of these women were treated with total mastectomy. In the remaining 33 percent, who were treated with partial mastectomy, the entire tumor was removed at the time of breast reduction. Fifty percent of the women were treated with radiation, and 25 percent were treated with chemotherapy or hormonal therapy. Compared with women in the general population of Ontario who have breast cancer, women whose breast cancer is discovered during breast reduction surgery are more likely to be treated with complete mastectomy and less likely to be treated with radiotherapy or chemotherapy. Seventy-one percent of the breast reduction group were axillary node-negative at diagnosis, compared with 58 percent in the general population of women with breast cancer. Survival from breast cancer in women diagnosed at the time of breast reduction (88 percent, 5-year survival) was better than survival from breast cancer in the general population (77 percent). These findings suggest that cancers found in women at the time of breast reduction are less advanced, possibly because they are diagnosed at an earlier stage.