Ira S. Goldenberg

Radiation therapy as initial treatment for early stage cancer of the breast wiithout mastectomy

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.

Prognostic factors in cancer of the female breast. II. Reproducibility of histopathologic classification

The reproducibility of histopathologic classification of breast tumor tissue (nuclear grade) and of axillary lymph nodes (sinus histiocytosis) has been evaluated. In 2 independent readings, an experienced observer assigned 70% of tumor tissue slides and 70% of lymph node slides to the same classification. Two other pathologists agreed fairly well with the classification by the experienced observer. Nuclear grade and sinus histiocytosis were found to be related to patient survival on the basis of classification by each of the 3 pathologists.

Radiation therapy as primary treatment for early stage carcinoma of the breast

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 mammary 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 followup ranging from 1–10 years. Only 1 patient has died from her disease; 1 has had a local recurrence readily controlled with mastectomy. Twenty‐six patients are alive 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 by clinicians. It deserves evaluation as a treatment option in randomized therapeutic trails.

Effect of age at first childbirth on risk of developing specific histologic subtype of breast cancer.

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 first 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.

Clinical trial of Δ1‐testololactone (NSC 23759), medroxy progesterone acetate (NSC 26386) and oxylone acetate (NSC 47438) in advanced female mammary cancer: A report of the cooperative breast cancer group

Three hundred and nineteen women with advanced and metastatic carcinoma of the breast were treated according to the protocol of the Cooperative Breast Cancer Group with one of three compounds: Δ1‐testololactone, micronized medroxy progesterone acetate or oxylone acetate. Drugs were supplied by the Cancer Chemotherapy National Service Center. NSC 23759: 17 alpha‐oxa‐D‐homandrosta‐1, 4‐diene‐3, 17 dione; NSC 26386: Pregna‐4‐ene‐3, 20‐dione, 17‐hydroxy‐6, alpha‐methyl‐, acetate; NSC 47438: 9 alpha‐pregna‐1, 4‐diene‐3, 20‐dione, 9‐fluoro‐11 beta, 17‐dihydroxy‐6 alpha‐methyl‐, 17 acetate. The oxylone produced 19.4% objective remissions, the progesterone 9.3% and the Δ1‐testololactone, 4.9%. Women who responded to therapy with any of these drugs had a better survival experience than those who did not since 50% of the responders were dead 21 months from the start of therapy but 50% of the non‐responders were dead 6 months thereafter. Although oxylone caused a moderate degree of difficulty with steroid effects, it might be considered effective therapy for advanced mammary cancer, especially as secondary therapy.

COMBINED ANDROGEN AND ANTIMETABOLITE THERAPY OF ADVANCED FEMALE BREAST CANCER A Report of the Cooperative Breast Cancer Group

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.

A dose-response evaluation of androgens in the treatment of metastatic breast cancer

A comparative double‐blind clinical trial of two androgens, one at two dose levels the other at three dose levels, in the treatment of metastatic breast cancer, was conducted by 10 members of the Cooperative Breast Cancer Group. The two androgens studied were dromostanolone propionate at 100 mg and 200 mg three times weekly and 7α‐methyl‐19‐nortestosterone acetate at 10 mg, 33 mg, and 100 mg weekly. The latter compound is a much more potent androgen and the hypothesis to be tested was whether or not a much more potent an androgen could induce a greater incidence of regressions. The rates of regression observed in this study were as follows: dromostanolone propionate at 100 mg, 22%, at 200 mg, 16% (the p value for the difference is 0.325); 7α‐methyl 19‐nortestosterone acetate at 10 mg, 15%, at 33 mg, 22%, and at 100 mg, 28% (the difference between the lowest and highest dose‐response rates being 0.05%). This study suggests that at least a log dose increase of a potent androgen is required to obtain an increased objective remission rate, whereas a one tenth of a log dose increase of a weaker androgen is not associated with an increased response rate. Abnormalities occurring during therapy with 7α‐methyl‐19‐ndrtestosterone acetate, whether drug‐and/ or disease‐related, decreased with increasing doses. The reason for this is not clear. No difference in total survival was observed between any of the treatment groups, but patients who had regressions had longer median survival than those who were classified as failures to therapy.

Secondary chemotherapy of advanced breast cancer

A randomized, protocol study by the Cooperative Breast Cancer Group has demonstrated the efficacy of chlorambucil, prednisone, hydrocortisone, and triiodothyronine as secondary therapy for advanced female breast cancer. Objective regression rates of 20.7% for chlorambucil and prednisone combined, 11.8% for hydrocortisone with triiodothyronine, and 9.8% for chlorambucil alone were defined. For the patient with advancing metastatic disease who has received initial hormonal therapy, it is recommended that further treatment with the combination of chlorambucil and prednisone be considered.

The effect of surgical resection of experimental “primary” adenocarcinoma of the colon on survival and incidence of metastases

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 di‐methylhydrazine‐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 inversely 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.