Screening for recurrent breast cancer--its effectiveness and prognostic value.

Performance of periodic follow-up examinations after mastectomy for breast cancer is standard practice, primarily for early detection and treatment of recurrence. This study was designed to determine whether this routine screening resulted in significant survival benefit for the patient. The medical records of 1,230 women treated for cure of invasive carcinoma of the breast were reviewed, and 248 cases of recurrence were identified for analysis. Only 36% of recurrences were discovered asymptomatically. Asymptomatic recurrence was associated with favorable biologic factors, ie, more frequent estrogen receptor (ER) positivity and initial node negative status, and survival was superior to that of others. This was particularly true for occult local recurrence. However, compliance with a present schedule of examinations did not confer superior survival. It was concluded that (1) routine screening after mastectomy detects few recurrences that are not already symptomatic, and (2) the superior survival associated with discovery of occult recurrence may result from the influences of lead time and length bias.

Estrogen receptors and breast cancer: prognostic and therapeutic implications.

From a review of clinical material, relationships were investigated between tumor estrogen receptors (ER) in breast cancers and (1) response of metastases to chemotherapy or endocrine therapy in 54 patients and (2) prognosis after mastectomy in 274 patients. Considering more than 300 femtomoles of ER per gram of tissue ER "rich" for premenopausal women and more than 700 ER rich for postmenopausal women, 14 of 20 patients (70%) with ER-rich tumors responded to endocrine therapy, whereas only one of 21 (4.8%) with ER-poor tumors responded. The probability of response appeared to increase with the concentration of ER. No correlation could be found between ER status and responsiveness to chemotherapy. Compared with patients with primary tumors poor in ER, those with ER-rich tumors had less recurrence after mastectomy, a longer free interval, and a more favorable disease-free survival, The 8S and 4S fractions of ER had similar relationships to tumor response and prognosis.

PIP: The predictive value of ER (estrogen receptor) for successful hormone and endocrine therapy, as well as for prognosis after mastectomy, has been reported. This paper reports the observations made by a hospital-based ER laboratory in the greater Milwaukee area using the sucrose density gradient assay method. Relationships between tumor ER in breast cancers and response of metastases to chemotherapy or endocrine therapy in 54 patients were investigated, as were prognosis after mastectomy. 14 of 20 patients with ER-rich tumors responded to endocrine therapy compared to only 1 of 21 with ER-poor tumors. Probability of response increased with concentration of ER. ER status did not correlate with responsiveness to chemotherapy. The 8S and 4S fractions of the ER protein correlated with hormonal responsiveness and prognosis. Patients with ER-rich tumors had less recurrence after mastectomy, a longer free interval, and a more favorable disease-free survival compared with patients whose primary tumors are poor in ER.

Prognosis of patients with breast cancer related to the timing of operation.

Whether the timing of mastectomy during the menstrual cycle influences the prognosis of premenopausal women with breast cancer is controversial. We retrospectively reviewed the cases of 97 regularly menstruating women treated for operable stages of breast cancer. At operation, 55 women were in the perimenstrual phase of the menstrual cycle (days 0 through 6 and days 21 through 36) and 42 were in the periovulatory phase (days 7 through 20). No relationship could be identified between the timing of surgical treatment and subsequent recurrence or survival. The timing of biopsy was also not associated with prognosis. We conclude that no delay of surgical treatment for breast cancer need be based on the phase of the menstrual cycle of premenopausal women.

Combined therapy for inflammatory breast cancer.

The prognosis for patients with inflammatory breast cancer has improved in recent years. This review was undertaken to evaluate current management in three Milwaukee (Wis) hospitals and to identify determinants of prognosis. We identified 25 patients with inflammatory breast carcinoma diagnosed between 1967 and 1987. Most of the patients were treated with combination chemotherapy and radiation therapy, and 10 had mastectomies. The 5-year survival of patients without initial distant metastases was 24%. The 5-year survival of patients who received chemotherapy before local treatment was 40%. Patients who had clinically involved axillary nodes or a palpable mass in the breast had poorer survival than those who did not; the presence of dermal lymphatic invasion had no significant effect on survival. Initial chemotherapy has become an important part of the care of patients with inflammatory breast cancer. It remains uncertain whether mastectomy improves on irradiation in achieving local control or improves survival.

Breast tumor incidence in rats after partial mammary resection.

The use of subcutaneous mastectomy in women at high risk for breast cancer is based on the assumption that surgical reduction of the tissue at risk results in a corresponding reduction in risk. To assess the validity of this assumption in an animal model, we subjected 120 female Sprague-Dawley rats to the mammary carcinogen 7,12-dimethylbenz(alpha)anthracene and a 20% fat diet. Two days later, one mammary ridge was excised in half of the animals (mastectomy group), and a midline incision was made without excision of tissue in the other half (control group). Seventy-nine rats survived dosing and operation and were observed for 77 weeks. After 15 weeks, 17 of 39 controls and seven of 40 animals with mastectomies had histologically confirmed neoplastic tumors of the breast. However, after 77 weeks, 32 of 39 controls and 35 of 40 animals in the mastectomy group had neoplastic tumors. The incidence of carcinogen-induced mammary neoplasms in rats progressed with time; whereas surgical reduction of breast tissue was followed by early reduction in neoplasias, the difference was not maintained.

Colonic neoplasms: tissue estrogen receptor and carcinoembryonic antigen.

Estrogen receptor protein was found in 24% of colonic neoplasms. Presence of estrogen receptor activity was independent of age or sex of the patient, state of differentiation or spread of the tumor, and concentration of carcinoembryonic antigen in the tumor. Estrogen receptor activity in colon tumors probably reflects novel protein synthesis resulting from dedifferentiation. Measurement of tumor estrogen receptor protein and carcinoembryonic antigen may have discriminatory value in the patient with metastatic adenocarcinoma and an unknown primary neoplasm.

Estrogen-receptor protein in intracranial meningiomas.

The increased frequency of meningiomas in women compared with men, and the rapidly progressive course of these tumors in pregnant patients suggest that hormones may be involved in this disease. Tumor tissue from six patients with meningiomas was analyzed for estrogen-receptor protein. Two patients had tumors with very high concentrations of this protein, approaching that found in hormonally sensitive breast carcinoma. The biochemical and possible clinical significance of these findings is discussed.

PIP: Because the epidemiology and clinical course of some meningiomas suggest that these tumors may be hormonally sensitive and that they may contain estrogen receptor protein, and because two-thirds of all intracranial meningiomas and 80% of all spinal meningiomas occur in women, the relationship between pregnancy (and its hormonal alterations) and development of these meningiomas was studied using tissue samples obtained from 6 patients with meningiomas. These samples were analyzed for estrogen receptor protein and were then correlated with preoperative and intraoperative observations. The 6 cases studies are presented, and the following results were apparent. Significant quantities of estrogen receptor protein were found in tissue from 4/6 patients (212 [ this patient was 10 weeks pregnant] , 62, 57, and 223 total receptors in fmol/gm.). Tumor tissue from 3/4 women and 1/2 men contained measurable estrogen receptor protein. The highest concentrations were found in 2 mid-30-year-old premenopausal women (1 of whom was 10 weeks pregnant). Common findings in these cases were premenopausal status, prominent tumor vascularity, and adjacent tissue invasion. The remaining female whose tissue sample showed estrogen receptor protein was classified as a perimenopausal woman based on a 6-month period of amenorrhea within the previous year. No significant estrogen-receptor activity was found in the cases of 1 man and 1 woman. The sedimentation coefficient of the estrogen receptor protein varied among the tissue samples. In 2 cases, the receptor protein was present in primarily the 4s fraction, whereas in the 2 other cases the concentration was greatest in the 8s sedimenting fraction.

Experience with pancreatoduodenectomy in a cancer hospital.

Records of twenty-nine patients with adenocarcinoma of the pancreas, ampulla of Vater, common bile duct, and colon who were treated with pancreatoduodenectomy were reviewed. Operative mortality was 24 per cent. Survival was adversely affected by incomplete excision of the primary lesion, the presence of metastases in lymph nodes, and severe biliary obstruction. Twenty-two patients (76 per cent) died from the operation or were not cured. Pancreatoduodenectomy was of dubious value in the treatment of carcinoma of the head of the pancreas.

The variability of estrogen receptors in metastatic breast cancer.

Estrogen receptor protein (ERP) concentrations were determined by the sucrose diffusion method in primary tumors and one or more metastases in twenty-nine patients with breast cancer. Concurrence of ERP concentrations between primaries and at least some metastases was found in 76 per cent of cases. Multiple metastases were assayed in ten cases, three of which demonstrated highly variable concentrations. It was concluded that clinically significant differences in ERP concentrations often exist between primary breast cancers and their metastases as well as between different metastases from the same tumor, accounting for the lack of responsiveness of some ERP-"positive" tumors and for mixed responses to hormonal or endocrine therapy. Assay of an isolated metastasis may be no more reliable in predicting overall patient benefit from therapy than assay of the primary itself.

Breast cancer in men.

Aside from its much lower frequency, breast cancer in men is remarkably similar to the disease in women. The cause remains equally obscure; the clinical presentation, pathology, and natural history are similar; and men are probably as curable in similar circumstances. Men are generally older and in more advanced stages than women when diagnosed, the tumors are located more often beneath the nipple and are more often responsive to hormonal therapy, but otherwise differences are negligible. Stage and axillary node status are strong prognostic indicators. Modified radical mastectomy has replaced radical mastectomy for surgical treatment of early states, and systemic adjuvant therapy appears to improve the prognosis for cases with involvement of lymph nodes.

Obesity, estrogen production, and tumor estrogen receptors in women with carcinoma of the breast.

The poor prognosis of obese women with carcinoma of the breast has yet to find a satisfactory explanation. It is suspected that the hormonal milieu of these patients may favor tumor growth. This investigation explored the relationship between obesity, urinary estrogen excretion, and tumor estrogen receptors (ER) in women treated with mastectomy for carcinoma of the breast. The ER levels determined from the primary cancers of 129 women treated with mastectomy were compared with the obesity index (O.I.) of these patients, i.e., weight in pounds/height in inches. In addition, 24-hour total urinary estrogen determinations were performed in 30 postmenopausal women and compared with their O.I. and ER. A weak direct correlation was found between ER and O.I. in postmenopausal women. The urinary estrogens of postmenopausal women were correlated directly with obesity index, but no relationship could be established between urinary estrogens and the ER content of breast cancers. It is concluded that the excess estrogen production of obese women may be responsible for their poor prognosis by promoting tumor growth. The high tumor ER concentrations associated with obesity suggest a high frequency of hormonally sensitive tumors.

Montgomery's areolar tubercle. A light microscopic study.

Conflicting impressions regarding the anatomy of Montgomery's areolar tubercle exist. Twelve modified radical mastectomy specimens provided 1,536 serial sections of areolar tubercles. In 34 of 35 tubercles (97%), a mammary lactiferous duct was associated with a sebaceous apparatus. This lactiferous duct ascended from deeper mammary parenchyma and entered the sebaceous gland. Histopathologic changes identified included featured of fibrocystic disease, atypical intraductal hyperplasia, and carcinoma in situ. Because the areolar tubercle has two components, a sebaceous gland and a mammary duct arising from deeper breast parenchyma, diseases of the breast may also involve the areola independent of papilla-nipple involvement. Areolar preservation may best be used with the knowledge that diseases underlying the areola may also involve the areola.

Establishment of a clinical teaching associates breast examination program for medical students.

A program was designed to instruct medical students on how to obtain a history pertinent to breast abnormalities and to perform a breast examination. The use of clinical teaching associates provides direct student instruction and critiques during the examination. In addition, students are taught how to instruct patients in the breast self-examination and to properly document breast abnormalities. Such a program should be considered for incorporation in all physical diagnosis courses as well as in residency training programs and seminars for practicing physicians.