Thomas L. Dao

Factors affecting recurrence in lumpectomy without irradiation for breast cancer

Between 1980 and 1988, 122 women with operable invasive breast cancers underwent wide excision and axillary dissection without subsequent irradiation. During the follow‐up period of 1 to 8 years (median, 4 years), recurrences were observed in 23 patients (19%), 22 occurring in the breast and one in the axilla. This is a significant rate of recurrence and supports the need for breast irradiation after conservative surgery. The incidence of recurrence in the breast did not appear to be related to the presence or absence of axillary nodal metastasis. No recurrences were noted in 20 patients whose primary tumors were smaller than 1 cm. The incidence of recurrence was directly correlated to the increasing size of the tumor, but it also appeared to decrease with advancing age. In 31 patients over 70 years of age, only one (3%) recurrence was observed. If these early findings are confirmed, it is likely that patients with tumors smaller than 1 cm or patients over 70 years of age may be spared breast irradiation after wide excision.

Steroid Sulfatase Activities in Human Breast Tumors

Summary The ability of human breast tumor preparations to hydrolyze DHEA, estrone, and testosterone sulfates was studied. Of the 85 tumor preparations examined, 31 tumors contained an estrogen sulfatase activity and 19 of which also exhibited sulfatase activity toward DHEA; but there was no testosterone sulfatase in any of the 31 tumor preparations. The remaining 54 tumor preparations showed no sulfatase activity toward any of the three steroid sulfates examined. The present data also disclose that the levels of sulfatase activities do not affect those of sulfotransferase activities in the tumor preparations. Further, the ratio of sulfotransferase activity with DHEA and estradiol as substrates is not related to the sulfatase activity in these tumor preparations.

Combination chemotherapy for metastatic breast cancer: comparison of multiple drug therapy with 5-fluorouracil, cytoxan and prednisone with adriamycin or adrenalectomy.

A prospective randomized clinical study to compare 3 treatment modalities, consisting of single‐agent chemotherapy with adriamycin, adrenalectomy, and combination chemotherapy with cytoxan, 5‐FU and prednisone (CFP), was carried out in 94 postmenopausal women with metastatic breast cancer. All of these patients had not received previous hormonal or cytotoxic chemotherapy, and all had measurable disease for response evaluation. Patients were randomized to one of three therapeutic arms: 1) adrenalectomy, CFP, adriamycin, in sequence, or 2) CFP, adriamycin, adrenalectomy, in sequence, or 3) adriamycin, adrenalectomy, CFP, in sequence. Objective response to initial therapy was seen in 9 of 26 adrenalectomy patients (35%), 12 of 32 adriamycin‐treated patients (38%), and 13 of 30 CFP‐treated patients (43%). Duration of remission was significantly better in CFP‐treated patients with a median duration of 21.3 months, as compared to adrenalectomy‐ or adriamycin‐treated patients, with median durations of 9.2 and 7.6 months, respectively. The evaluation of the overall palliative achievement of the three fixed arms, based on response to at least one modality was 13 of 26 in the adrenalectomy sequence (50%), 13 of 30 in the CFP sequence (43%), and 18 of 32 in the adriamycin sequence (56%). There was no response to secondary or tertiary therapies among patients receiving CFP as the initial treatment. The data show that combination therapy with cytotoxic and hormonal agents is superior to single‐agent therapy of adrenalectomy. However, the results also disclose that there is no therapeutic advantage in using CFP as an initial therapy in women with advanced breast cancer.

Aminoglutethimide in patients with metastatic breast cancer

Aminoglutethimide (AG) was administered as palliative therapy in 112 patients with metastatic breast cancer. In 36 patients, the dose level was 1000 mg/day; 76 patients received a dose level of 500 mg/day. Patients with brain or liver metastasis were excluded, as were patients with tumors determined to be negative for estrogen receptors. Objective regression was observed in 35(31%) patients, with the duration of response ranging from 4 to 36+ months (mean, 12 months; median, 10 months). Response was observed in 11 of 31(35%) patients with soft tissue metastasis; 16/59 (27%) patients with osseous metastasis; and 8 of 22(36%) having visceral metastasis. In 93 patients with positive estrogen receptor (ER), 33 responded (35%), whereas in 19 patients with unknown ER status, two responded (11%). Response to previous treatment with tamoxifen (TAM) had occurred in 31 patients; of these, response to AG was noted in 11 (35%). Of 24 patients failing to respond to prior treatment with tamoxifen, four (17%) responded to subsequent therapy with AG. Thirteen patients had previously received combination chemotherapy, and response to AG was noted in two (15%). The side effects observed in this study included skin rash in ten patients, fever in eight, somnolence in three, weakness and dizziness in one, headache in one, insomnia in one, dyspnea in one, and ataxia in one. Treatment had to be discontinued in eight patients, due to the severity of the side effects. As expected, patients receiving AG at the lower dose level of 500 mg/day experienced fewer and less severe side effects than those treated with the higher dose. The response rate in the 1000 mg/day group was 10/36 (28%) and in the 500 mg/day group, it was 25/76 (33%). The lower dosage was better tolerated without apparent compromise in therapeutic efficacy.

Tamoxifen (nolvadex) versus adrenalectomy in metastatic breast cancer

The relative efficacy of adrenalectomy and tamoxifen (Nolvadex) was evaluated in a randomized study of 51 patients with metastatic breast cancer. In 25 patients undergoing adrenalectomy, there were 13 responders. There were 9 responders of 26 patients receiving tamoxifen. There was no statistically significant difference. In the crossover phase, 15 patients received tamoxifen following adrenalectomy and 3 responded, one of the 6 previous adrenalectomy responders and 2 of the 9 adrenalectomy non‐responders. Nine patients underwent adrenalectomy following tamoxifen, and there were five responders, one of two tamoxifen responders and four of seven tamoxifen nonresponders. Both tamoxifen and adrenalectomy were effective modalities, and appear to retain effectiveness in crossover trials. The frequency of remission was similar in both groups treated by both modalities in different sequences. Response rates to adrenalectomy, considered as both primary and secondary therapy, were significantly higher, since 18 of 34 patients (53%) responded to this therapy, whereas 12 of 41 (29%) responded to tamoxifen as either primary or secondary therapy. Cancer 53:1333‐1335, 1984.

Urinary Excretion of Estrone, Estradiol, and Estriol in Postmenopausal Women With Primary Breast Cancer

The daily excretion of estrone, estradiol, and estriol was determined for 22 normal women and 35 women with primary breast cancer. The excretion of the hormones (measured in microgram/24 hr) in the breast cancer group was elevated and showed a statistical significance of P less than 0.001. The same wide difference between the 2 groups was also noted when excretion was expressed in terms of the body area of the individuals and when women of similar ages were compared.

Is modified radical mastectomy adequate for axillary lymph node dissection

The effectiveness of axillary dissection by modified radical mastectomy was assessed by a comparison of the total axillary nodes removed by this operation to that by radical mastectomy. In a series of 121 consecutive radical mastectomies performed during the period of 1964 to 1969, we found that the number of axillary nodes removed ranged from 3 to 63 with a median of 22 and a mean of 23.4 per patient. In a subsequent series of 111 consecutive modified radical mastectomies performed between 1969 and 1973, the total axillary nodes removed ranged from 6 to 77 with a median of 24 and mean of 25.7 nodes in each mastectomy specimen. These results strongly suggest that axillary dissection in modified radical mastectomy is as complete as that in the Halsted radical mastectomy.

Therapeutic oophorectomy in metastatic breast cancer

One hundred five patients undergoing therapeutic oophorectomy for metastatic breast cancer (n = 105) from 1975 to 1985 were reviewed. There were 54 responders (51%) to oophorectomy, with a median duration of response of 16 months (range, 3 to 129 months). Thirty of 42 (71%) estrogen receptor (ER)‐positive patients responded to oophorectomy versus five of 24 (21%) ER‐negative patients (P < 0.001). Of the 39 patients with unknown ER status, 19 (49%) responded to oophorectomy. Osseous, soft tissue, and pulmonary metastases responded at similar rates. Of the 16 patients who had received adjuvant chemotherapy, there were five responders (31%) to oophorectomy. Second‐line endocrine therapy was effective in 29 of 53 (55%) patients. Fifteen of 28 (54%) ER‐positive patients responded to second‐line endocrine therapy while two of six (33%) ER‐negative patients responded. Twenty‐three of 37 (62%) oophorectomy responders responded to second‐line endocrine therapy versus six of 16 (38) nonresponders. Oophorectomy appears to be a valuable palliative treatment for metastatic breast cancer. ER‐positive patients have the best chance of responding to this therapy. However, ER‐negative patients have a reduced but definite chance of responding with a good duration of response. Response to further endocrine treatments is predicted by response to oophorectomy and to a lesser degree by ER status.

Adrenalectomy with radical mastectomy in the treatment of high-risk breast cancer.

Bilateral adrenalectomy with radical mastectomy has been performed in a series of 17 postmenopausal women with breast cancer having metastasis in four or more axillary lymph nodes. Results to date show that both the recurrence and mortality rates are significantly lowered in this group of “high‐risk” breast cancer patients by the combined treatment. Of these 17 patients, 14 are living and well with no evidence of disease. Six are surviving without recurrence 5 or more years since their primary treatment. The study also demonstrated that adrenalectomy patients on hormone replacement therapy are able to lead full and active lives for a long time without complications. This pilot study should be considered as a guide to future clinical trials rather than as an immediate recommendation for general therapy.

Protection of estrogenic hormones by ascorbic acid during chromatography

Abstract Oxidative decomposition of phenolic hormones during thin-layer chromatography can be avoided by the incorporation of ascorbic acid into the plates. The application of this technique to the purification of urinary extracts is described.