THE exact metabolic interrelationships between the thyroid and the adrenal cortex have been subject to many varying interpretations. Experimental evidence from animal investigations suggests that adrenocortical products are antagonistic in some way to thyroid hormone, as demonstrated by a decrease in nitrogen excretion following the administration of adrenocortical hormone to dogs previously rendered hypermetabolic by the ingestion of thyroxin (1). The present study was designed to evaluate several metabolic activities in 2 patients at varying levels of thyroid and adrenocortical function in a controlled environment. The first subject (E.McC.) was a hypothyroid female with presumably normal adrenocortical function, who was studied to determine the metabolic effects of maximal adrenocortical stimulation (by exogenous ACTH) during periods of hypothyroidism and hyperthyroidism. The second subject (M.H.) was a euthyroid male with hypoadrenocortical reactivity, as shown by lack of response to the ACTH-eosinophil test (Thorn). He was studied to ascertain if any metabolic changes were induced by administration of aqueous adrenocortical extract during periods of depressed and elevated thyroid function.

The association between use of oral contraceptives and fibrocystic breast disease was assessed among women aged 20-74 years in a hospital-based case-control study conducted between November 1979 and November 1981 in Connecticut. The study groups comprised 633 women with biopsy-proven fibrocystic breast disease and 1,062 controls who had been admitted, as inpatients or outpatients, to general surgical services. For the premenopausal women, there was no evidence that long-term use of oral contraceptives was associated with a decreased frequency of fibrocystic breast disease among either current or past users. For the postmenopausal women, previous oral contraceptive exposure was associated with an increased occurrence of cystic disease. These findings contradict previous investigations reporting a negative association between oral contraceptive use and the development of fibrocystic breast disease.

The relationship between use of oral contraceptives and fibrocystic breast disease was examined in a hospital-based case-control study undertaken in New Haven, Connecticut, from 1977 to 1979. Particular emphasis was placed on the extent of epithelial atypia and other histopathologic characteristics found in the biopsy specimens from the cases. Women who had ever used oral contraceptives were at a somewhat decreased risk for fibrocystic disease as a whole. Cases with high atypia and controls had similar patterns of oral contraceptive use, whereas cases with low and intermediate atypia had less oral contraceptive use than controls. Cases with intermediate atypia reported the lowest oral contraceptive use. Subjects with biopsy specimens exhibiting gross cysts, microscopic cysts, or papillomatosis were about 50% less likely to have used oral contraceptives than controls.

Epidemiologic variables related to breast cancer risk were assessed in a case-control study of 332 women with breast carcinoma and 1353 comparison women. Risk factors for breast cancer as a whole included nulliparity, late age at first childbirth, early age at menarche, late age at menopause, personal history of benign breast disease, family history of breast cancer, and among postmenopausal women, body weight. These risk factors were then analyzed with respect to histologic subtype of breast cancer involved, i.e., duct-derived or lobular tumors, to determine whether the association between any of the risk factors and breast cancer varied according to histopathologic subtype. Histologic subtype for the 316 cases reviewed included 284 duct cancers and 32 lobular carcinomas. Although slight differences were noted among some of the risk factors and the variety of cancer, none of the differences was marked except for the variable age at birth birth. For ductal carcinoma, the risk was highest among nulliparous women and decreased the younger a woman was at the time she gave birth to her first child. The risk of infiltrating lobular carcinoma, however, was lowest among nulliparous females or those who had given birth at a young age and increased the older a woman was when she gave birth to her first child.

In a hospital-based case-control study of the epidemiology of breast cancer undertaken in Connecticut from 1977 to 1979, there was no evidence of an increase in risk for breast cancer among women who had used oral contraceptives or estrogen-replacement therapy. In fact, there was some suggestion of a decrease in risk for breast cancer with increasing length of use of oral contraceptives. Higher than average risks were found among women who had never give birth to a child, women with a late age at menopause, women, with an early age at menarche, women who had given birth to their first child at a relatively late age, women with previous benign breast disease, and women with a history of breast cancer in a sister or mother. Heavy women were at high risk for premenopausal breast cancer. The association between heaviness and postmenopausal breast cancer was strongest among women who had had their last menstrual period more than 5 years before the diagnosis of breast cancer.

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A reasonable alternative to mastectomy for women with early stage breast cancer is wide local excision of the lesion coupled with radical radiation therapy. The recurrence and longevity results with this method have been as good as, if not better, than standard mastectomy after 10 years' clinical experience in a limited number of patients. The physical and psychological impact of this therapy is more acceptable than mastectomy to the woman with breast cancer in its earliest stages.

The series of books entitled "Major Problems in Clinical Surgery" has established an excellent reputation dealing with such diverse topics as portal hypertension, liver trauma, surgery of the aged, and tumors of the large bowel, to mention only a few of the subjects previously discussed. The fifth and latest volume in this series is the second edition ofCancer of the Breast, and the new edition continues the excellence of the first publication in 1967. Breast cancer remains a major problem facing the surgeon despite some 3,500 years of recognition of the disease process. Etiology and pathogenesis remain unclear, and conflicting therapeutic ideas plague both patient and physician. This volume addresses all aspects of breast cancer in a complete fashion, emphasizing the unknown as well as the accepted and allowing all viewpoints an opportunity for expression. The contributing authors do not try to promulgate a single viewpoint, but allow the

Stage I carcinoma of the female breast can be treated effectively by total mastectomy and post-operative radiation therapy to the chest wall and regional lymph nodes. Identification of positive axillary lymph nodes for prognostic purposes or for definition of patients who might benefit by adjuvant chemotherapy is not a requisite to the successful management of early stage carcinoma of the breast.

The effect of surgical resection of "primary" tumors classified by size at the time of resection has been studied in two tumor cell lines derived from dimethylhydrazine-induced colonic neoplasms in the Buffalo strain rat. Surgical treatment of colon cancer in the rat yields results similar to those for human carcinoma. Some of the smallest tumors resected were associated with metastases and this finding suggests a need for effective postoperative adjuvant therapy. The incidence of metastases and the size of the tumor were inveresely related to survival, e.g., the smaller the tumor or the sooner the excision, the greater the survival of the animal. The operated animal model studied here could prove to be very useful for evaluating various forms of systemic therapy for the control of micrometastases associated with colonic neoplasms.

This report describes 150 patients with clinical stage I and II carcinoma of the breast treated at four institutions--Yale University School of Medicine, Harvard Medical School-Joint Center for Radiation Therapy, Hahnemann Medical College, Jefferson Medical College--with radiotherapy only following excisional biopsy. Closely similar treatment policies were followed at all four centers, 4500-5000 rads minimum tumor dose being delivered to the entire breast and axillary, supraclavicular and internal mammary nodes. Forty-six of 49 stage I patients treated are alive without disease, the actuarial relapse-free survival being 91% at 5 years. Of the 101 stage II patients, 75 are alive without disease with a relapse-free actuarial survival of 60% at 5 years. Local failure has occurred in 10 patients (9 stage II and 1 stage I, 6.6%) 5 of whom are disease-free following mastectomy. The results obtained in this study are comparable to those of conventional surgery. It is our conclusion that mastectomy is not a necessary part of the treatment of small breast cancers, that radiation without mastectomy is an acceptable alternative with far superior cosmetic and functional results. Adjuvant chemotherapy should be considered particularly in stage II patients in view of their 40% relapse rate.

A clinical trial of androgen and antimetabolite therapy of advanced female breast cancer was conducted in 110 patients by the Cooperative Breast Cancer Group. An objective regression rate of 20% was achieved in women receiving oral testolactone, 6% in patients given intravenous fluorouracil alone, and 14% when the androgen and antimetabolite were administered together. This randomized trial according to the CBCG protocol did not produce the high regression rate noted previously in a nonrandomized, nonprotocol evaluation of these drugs.

Experience with 50 women undergoing extracranial transethmoidal-sphenoidal hypophysectomy for metastatic breast carcinoma with 12-month follow-up showed an objective remission of metastases after hypophysectomy in 58% of patients. The highest incidence of remission following the operation occurred in those women with only osseous metastases (83%) or with previous remission to both therapeutic oophorectomy and androgen administration (86%). No patient with primary central nervous system metastases, only one of ten with hepatic metastases, and none who had failed to respond to both oophorectomy and exogenous androgen administration experienced remission after hypophysectomy. The operative approach to the pituitary was via a periorbital incision, the posterior ethmoid cells, and the sphenoid sinus. Cerebrospinal fluid rhinorrhea occurred in three early patients, and has been successfully avoided in later ones by a fascia lata graft. Diabetes insipidus, seen in 13 patients, and extraocular palsies, seen in two, were transient.

A treatment program for early stage breast cancer consisting of biopsy only and primary radiation therapy is described. The treatment plan is "radical" with tumoricidal doses or radiation delivered to the breast and axillary, supraclavicular, and internal mammory lymph nodes, i.e. 6000-7000 rads to clinically involved areas and 4500-5000 rads to subclinical disease. Thirty patients have been treated with this program, with followupranging from 1-10 years. Only 1 patient has died from her disease; 1 has had a lot oflocal recurrence readily controlled with mastectomy. Twenty-six patients arealive and well; there have been 3 deaths from intercurrent illness. No significant radiation complications have occurred. Radiation therapy as the sole treatment for breast cancer has been described in the literature for at least 20 years but generally ignored byclinicians. It deserves evaluation as a treatment option in randomized therapeutic trails.

The results in 362 postmenopausal women with advanced breast cancer treated with delta-1-testololactone according to the protocol of the Cooperative Breast Cancer Group are reported. Delta-1-testololactone is 17a-oxa-d-homo-14-androstadine-317-dione (Teslac NSC 23759) a hormonally inactive testosterone derivative. It does not produce masculinization in women nor significant metabolic changes in test animals. Regression of metastatic breast cancer with this agent has been reported in 12.5-30% of cases. In this study the drug was administered at levels of 200 mg 1000 mg and 2000 mg per day. Treatment was stopped in 11 patients because of toxicity 14 refused to continue and 2 were lost to followup. A total of 33 untoward effects involving 29 of the 362 patients were reported mostly gastrointestinal. No deaths resulted from toxicity of the drug. Few of the reactions were severe. With the 200 mg dose there were 4.2% remissions; with 1000 mg 14.6%; and with 2000 mg 12.4%. Side-effects were lowest with the 1000 mg dose. The difference between 200 mg and 1000 mg doses in remission rates was significant at the p<.01 level between the 200 and 2000 mg level at the p<.05 level. Those responding clearly lived longer than those not responding; 91% with objective regressions were alive 12 months after starting treatment. With visceral metastases the 2000 mg dose is recommended for those not responding to the 1000 mg dose.