Edwin D. Savlov

The relative importance of estrogen receptor analysis as a prognostic factor for recurrence or response to chemotherapy in women with breast cancer

The value of estrogen receptor (ER) analysis in primary breast cancer samples as a potential prognostic factor was examined in three clinical situations: time to recurrence in patients with no therapy after mastectomy, failure of patients receiving adjuvant therapy, and response of advanced disease patients to cytotoxic chemotherapy. Other prognostic factors analyzed were menopausal and nodal status. In none of these clinical settings were we able to demonstrate the usefulness of ER status as a prognosticator of the disease course or its response to therapy.

Radiozinc studies in experimental wound healing

Summary Studies of radiozinc retention in experimental wound healing have been carried out in rats with incised abdominal wounds and excised back wounds. A prefeential accumulation of radioctivity was demonstrated in the acute healing stage of incised wounds, coinciding with the development of vascularity and biochemical alterations. Measurements made on the scar connective tissue of the excised wounds after 100 days showed very low retention of radiozinc compared to the surrounding skin and hair.

Correlations between certain biochemical properties of breast cancer and response to therapy: A preliminary report

Biochemical analyses were carried out on tissues from 130 women with mammary carcinoma and 104 patients with benign breast lesions. The tissues were assayed for specific estrogen‐binding proteins (EBP) and for several enzymes involved in carbohydrate and lipid metabolism. Normal breast, fibrocystic disease, and fibroadenomas usually exhibited lower enzyme levels than malignant tissues, and rarely contained specific EBP. Intraductal carcinoma appears to contain certain biochemical characteristics unique to this tissue when compared with benign proliferative breast diseases; these differences may be of value in prediction of response to various types of therapy.

The lack of relationship between estrogen receptor status and response to chemotherapy

The possible relationship between estrogen receptors and response of breast cancer patients to chemotherapy was examined in two situations: patients with advanced disease and patients receiving postsurgical adjuvant treatment. In 73 patients with disseminated disease, no relationship between ER status and response to cytotoxic chemotherapy was observed. At this time, 44 of these cases have undergone extramural review; in these 44 cases, we observed no significant relationship between ER status and response to chemotherapy. In a series of 52 patients receiving adjuvant therapy, 27 patients were classified as failures due to recurrence. ER status did not offer prognostic value for failure of patients treated with postsurgical adjuvant therapy. We conclude that the prognostic value of ER data in nonhormonal therapy settings remains to be proven.

Treatment of metastatic breast cancer with aminoglutethimide

Seventy‐three women with metastatic breast cancer were treated with aminoglutethimide and dexamethasone. No complete responses occurred. Ten patients (16%) achieved partial responses (mean duration, 12 months). The proportions of patients responding by disease site were breast (50%), nodes (33%), skin (23%), bone (16%), lung (11%), and liver (7%). Response did not correlate with age, menopausal status, performance status, or cortisol suppression. Ninety percent of responders had had previous responses to hormonal manipulations. No responses occurred in estrogen receptor negative patients. An additional 20% of patients had disease stabilization of eight or more months (mean, 17 months). Severe bone pain was present in 47 patients and was relieved in 19. Side effects occurred in 75% but caused discontinuation of therapy in only four patients. Somnolence, nausea, rash, Cushings syndrome, and leukopenia were the most frequent side effects. Aminoglutethimide with dexamethasone is an effective hormonal treatment for metastatic breast cancer.

Peritoneovenous shunt for palliation of malignant ascites

Forty patients with malignant ascites refractory to conventional medical management had peritoneovenous shunt for palliation. The shunt provided effective palliation in 28 with decrease in weight, abdominal girth, number of paracenteses required and increase in urine output. These patients also had improvement in strength, appetite and ambulation. Complications such as hemodilution, volume overload, and sepsis do not contraindicate surgery. In 12 patients with high ascitic fluid protein content (4.5 g/liter) and a large number of malignant cells, loculated ascites and prior severe renal and cardiac disease, the shunt did not provide palliation. Peritoneovenous shunt appears to provide effective palliation in carefully selected patients with refractory malignant ascites.

Further studies of biochemical predictive tests in breast cancer.

This report extends our observations on the relationship between the therapy of breast cancer, estrogen binding and tissue enzymes. We have compared the dextran‐coated charcoal method and the sucrose gradient analysis in determining estrogen receptors, and find a sub‐group of receptor positive tumors—identifiable only by the latter technique—which we suggest may lead to an incorrect prediction of response to hormonal therapy. Data are also presented to suggest that enzyme analyses show promise in predicting responsiveness to present modes of combination chemotherapy of breast cancer.

Low tissue enzyme activity seen in breast cancers of patients who fail adjuvant chemotherapy.

Primary breast cancers from 54 patients undergoing postsurgical adjuvant chemotherapy were analyzed for several enzymes and estrogen receptors to determine if biochemical parameters might offer a prognostic index for determining outcome of therapy. Recurrence of disease during therapy or within 12 months after cessation of therapy was the criterion for classifying the patient as a treatment failure. Recurrence rates were similar in ER‐positive vs. ER‐negative patients, indicating that estrogen receptor status offered no predictive value in this series. However, patients who failed therapy had tumors that displayed significantly lower activities of lactate dehydrogenase, glucosephosphate isomerase, and glucose 6‐phosphate dehydrogenase vs. patients who showed no evidence of recurrence for this observation period. When either premenopausal or ER‐negative patients were compared, a similar observation was made; low enzyme activities occurred in patients failing to benefit from adjuvant chemotherapy. Based on this series of patients, it is suggested that a selected enzyme activity profile may offer a predictive index for recurrence in the adjuvant chemotherapy setting.

Relationship of glycolytic enzyme activities and response of breast cancer patients to chemotherapy. A preliminary report

Activities of glucosephosphate isomerase, lactate dehydrogenase, and NADP‐isocitrate dehydrogenase were significantly elevated in breast cancer specimens from patients who responded favorably to combination cytotoxic chemotherapy regimens compared with those in carcinomas from patients failing to respond to the same chemotherapy. Presence of estrogen receptors and clinical response to hormonal therapy were also evaluated in neoplasms from these patients. The data suggest that measurement of the enzyme profile, along with estrogen receptor levels, may be useful in selecting a mode of therapy for patients with advanced disease.

A logistic model based on enzyme activities for the prediction of response of breast cancer patients to chemotherapy

A logistic regression model, utilizing the activities of certain selected glycolytic enzymes and ER status measured on primary or recurrent lesions, has been applied to predict for response to combination chemotherapy regimens administered to women with advanced breast cancer. The clinical outcome of response or no response was evaluated retrospectively using criteria employed by cooperative group protocols. In 93 cases, 58/61 patients classified as nonresponders and 22/32 patients demonstrating objective responses would have been correctly designated, based on the 50% estimated probability as the level for separation of responders from nonresponders. The overall predictive accuracy of this model was 86%, with apparently greater accuracy for prediction of lack of response. Addition of estrogen receptor status to the model imparted no gain in accuracy of prediction. Application of this model to a prospective study is warranted. Cancer 50:1734‐1738, 1982.