Bilateral breast cancer.

Bilateral breast cancer has a cumulative incidence of 7% to 20% in patients with primary operable breast cancer, and the majority of these lesions are metachronous. A consensus on the management of the contralateral breast has been elusive. Much of the confusion arises from the fact that there exist marked differences of opinion regarding the impact of a second primary breast cancer on the overall prognosis. The risk of developing a contralateral breast cancer is influenced by the age of the patient, the presence of in situ disease, lobular histology of this new lesion, multicentricity, exposure to certain types of ionizing irradiation, and, possibly, family history of breast cancer. Management options include observation (clinical and mammographic surveillance), contralateral biopsy, and, rarely, prophylactic mastectomy. It is hoped that trials of breast cancer prevention, employing drugs such as tamoxifen, will identify agents capable of abrogating the risk of contralateral breast cancer and improve the ultimate outcome.

Breast carcinoma in situ.

A total of 150 patients with in situ breast cancer were treated from 1970 through 1976, with a median follow-up of 11.5 years. There were 42 patients with microinvasion and 25 with bilateral disease, analyzed separately. Eight patients who became unavailable for follow-up within five years (but who had no evidence of disease [NED]) were excluded. Eighty-five patients had ductal carcinoma in situ, 43 had lobular carcinoma in situ, and 22 had a mixed type. Modified radical mastectomy was done in 112 cases. One of 128 patients had positive axillary nodes; axillary dissection is not indicated for in situ breast cancer. Of the 150 patients, one with ductal disease died of disease. Six died of other causes, free of disease. Of 18 treated by excision alone, two underwent mastectomy for recurrence and had NED. Patients with microinvasion had involved nodes in 10%, and 94% had NED. However, all bilateral cases had NED.

Chemohormonal therapy and endocrine function in breast cancer patients.

The administration of CMFVP (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone) results in profound alterations in hormonal profiles of premenopausal women due to a reduction in ovarian and adrenal secretion of estrogens and androgens. Cytotoxic chemotherapy results in ovarian suppression as documented by decreases in estradiol with concomitant elevations in pituitary gonadotrophins, whereas the addition of prednisone to the cytotoxic regimen results in significant decreases in androgen levels due to adrenal suppression. In postmenopausal women, CMFVP also results in significant decreases in estrogens and estrogen precursors due to suppression of adrenal steroid metabolism. Continuous low-dose prednisone administration during cytotoxic chemotherapy appears to be more effective than an intermittent high-dose schedule in achieving and sustaining adrenal suppression. However, complete elimination of adrenal steroidogenesis does not occur in all cases since measurable amounts of adrenal steroids remain in the serum throughout chemohormonal therapy. The administration of tamoxifen plus CMFVP is associated with hyperestrogenemia in younger premenopausal patients which persists until the onset of ovarian suppression.

Survival in bilateral breast cancer.

The presence of bilateral invasive breast cancer places the patient in a state of double jeopardy. At Memorial Sloan-Kettering Cancer Center, the overall 10-year recurrence rate for unilateral Stage I breast cancer was 16%, whereas the recurrence rate for simultaneous, bilateral Stage I breast carcinoma was 29%: almost twice as high. The average 10-year survival of all patients with negative axillary nodes was 57%. In this retrospective analysis of 403 patients with bilateral primary operable breast cancer treated at Memorial Sloan-Kettering Cancer Center, significant differences were noted in the disease-free survival between patients with bilateral noninvasive cancer, bilateral invasive cancer, and the combination of invasive and in situ cancers. Bilateral intraductal cancer and lobular carcinoma in situ offered an excellent prognosis. The combination of preinvasive cancer on one side and infiltrating carcinoma on the other had the next best survival. The in situ lesion, when treated by mastectomy, did not alter the patients' life expectancy from that of the general population with unilateral breast cancer, thus indicating that surgeons should strive to detect breast cancer in its preinvasive form. The 5- and 10-year relapse-free survival of patients with bilateral invasive disease, regardless of axillary nodal status and tumor size, was 60% and 51%, respectively, for patients with a bilateral presentation and 54% and 38%, respectively, for carcinomas presenting metachronously. More important in determining prognosis, however, was the number of axillary nodes involved and the level of involvement. Invasion of bilateral axillary nodes at all levels predicted a poor prognosis. Because of this shortened survival, systemic adjuvant therapy should be considered for patients with bilateral invasive disease. The most common preinvasive breast cancer was lobular carcinoma in situ and the most frequently invasive tumor was infiltrating duct cancer. Since a contralateral breast cancer at the time of definitive treatment of the first side does not always present as a mass or with positive mammography, a random biopsy of the second breast is recommended. This should be done in the upper, outer quadrant and should include the subareolar area. With prompt adequate treatment, it is expected that survival from bilateral breast cancer should improve.

Endocrine consequences of CMF adjuvant therapy in premenopausal and postmenopausal breast cancer patients.

The effect of CMF adjuvant therapy (cyclophosphamide, methotrexate, and 5-fluorouracil) on endocrine function was investigated in breast cancer patients. CMF therapy resulted in suppression of ovarian function in some premenopausal patients but pituitary function and adrenal function were unaffected. There was an inverse relation between age and duration of treatment required to induce ovarian suppression. Although amenorrhea was achieved within 2-4 months in patients aged 40 years or older, younger women required larger cumulative doses of cytotoxic drugs to induce ovarian dysfunction. Patients younger than 30 years of age continued to menstruate with no major alteration in hormonal levels resulting from the cytotoxic drugs. CMF therapy had no significant effect on hormonal levels in postmenopausal patients indicating that in this group therapeutic response is not mediated via the endocrine system.

Serum lipid-bound sialic acid as a marker in breast cancer.

The reliability of lipid-bound sialic acid (LSA) as a marker in breast cancer was evaluated in 78 normal subjects, 106 patients with benign breast disease, 64 patients with primary operable breast cancer, and 61 patients with recurrent metastatic breast cancer. LSA levels were determined before and after mastectomy and during chemotherapy in selected patients to determine the value of LSA in monitoring therapy and predicting response. LSA levels greater than 20 mg/dl were not seen in normal subjects but were present in patients with benign breast disease (13%), primary breast cancer (47%) and recurrent metastatic breast cancer (62%). LSA levels decreased after initiation of chemotherapy and remained low in patients clinically disease-free. Recurrences were associated with elevated LSA in patients failing chemotherapy or endocrine ablative surgery. LSA measurements appeared to be of limited value in the detection of breast cancer but serial measurements may be useful in assessing disease progression and identifying patients resistant to therapy.

Axillary micro- and macrometastases in breast cancer: prognostic significance of tumor size.

Recurrence and survival data at 10 years were examined for 147 women with single axillary lymph node metastases found in a modified radical or standard radical mastectomy. The cases were identified through a review of all patients with primary operable breast cancer treated at Memorial Hospital from 1964 to 1970. The patients were stratified into groups according to size of the primary tumor and of the metastatic deposit (micro less than or equal to 2 mm; macro greater than 2 mm) as well as level of the positive node. In the entire series, there was a significantly poorer prognosis among those patients with single macrometastases (30/77 patients; 39% recurrence rate) when compared with those having micrometastases (17/70 patients: 24% recurrence rate). A major prognostic difference emerged after stratification by tumor size. Within the first six years of the follow-up period, T1 patients with negative nodes and those with single micrometastases had similar survival curves, significantly better than those with macrometastases. However, at 12 years, the survival rats of those patients with either a micro- or macrometastases was nearly identical, and significantly worse than for those patients with negative lymph nodes. On the other hand, among women with primary tumors 2.1-5.0 cm (T2), patients with negative lymph nodes or single micrometastases had survival curves that did not differ significantly throughout the course of the follow-up period. Both had an outcome significantly better than observed for patients with macrometastases. These findings have important implications for our understanding of the clinical behaviour of breast cancer and for the stratification of patients entered into randomized treatment trials.

Stage III carcinoma of the breast. A detailed analysis.

A ten-year study of Stage III breast carcinoma has been reviewed in detail. The single most dominant variable was axillary nodal involvement. Four hundred and thirty patients had nodal metastases, 58 patients did not. Four hundred and thirty patients with axillary nodal involvement had fiveand ten-year recurrence rates of 68 and 77%, while the survival rates were 41 and 21%, respectively. Life span was influenced by extent of nodal disease, being best for those with micrometastases only, and worse for those with four or more positive nodes. Skin edema, infiltration, or ulceration in the positive node group were grave signs. Muscle invasion or node matting, however, did not appear to influence length of life. Postoperative prophylactic therapy did not appear to affect survival rates. Radiation therapy alone did not influence either local recurrence or survival rates. Not enough time has elapsed to evaluate the results of postoperative chemotherapy. Patients who underwent oophorectomy and radiation therapy appeared to do better, but the number of patients was small. Of the 58 patients without nodal invasion, 82% were alive at five years and 75% were alive at 10 years. Grave signs did not influence the survival rate in this group. While the majority of patients with Stage III carcinoma had unfavorable variables, there were some patients who demonstrated a low recurrence rate and a long survival time. Aggressive treatment should be designed to save those patients who can be helped and to improve those patients whose life expectancy is limited. There is no place for timid initial treatment whether by operation or by irradiation. It must be given with intent to cure even though palliation is most often attained.

The problem of carcinoma developing in a fibroadenoma: recent experience at Memorial Hospital.

Fourteen new cases of unsuspected carcinoma developing in fibroadenomas are reported with a detailed analysis of their preoperative findings; histopathology, the results of varying surgical procedures and a three month to twenty-six year follow-up. The majority of lesions were lobular carcinoma in situ (71%) and 29% of all cases were found to have carcinoma of the contralateral breast. Our study suggests that for invasive carcinoma within a fibroadenoma complete mastectomy is warranted in virtually all instances while noninvasive disease treated by complete mastectomy is essentially curative. Contralateral breast biopsy at the time of diagnosis with a careful life-time follow-up are appropriate because of the high risk of contralateral invasive coarcinoma. There seemed to be no evidence of striking or unusual epithelial hyperplasia in the breast tissue adjacent to fibroadenomas that contained carcinoma suggesting that the carcinomas are not intrinsically different from those not related to fibroadenomas.

Primary inoperable cancer of the breast.

In a retrospective study of 305 patients with primary inoperable cancer of the breast, the over-all survival rate at five years was 12 per cent for those presenting with extensive lesions of the breast alone and 5 to 7 per cent for those with distant metastases. There was little difference in the survival times for any group within the study. Primary inoperable remains a useful classification for predicting prognosis. All survival curves suggested that distant metastases were present when the patients were first seen, whether obvious or not, and early use of combination chemotherapy for all patients is encouraged. Radiation therapy was the most effective treatment in terms of survival times for patients with local lesion. Palliative mastectomy after radiation therapy increased local control but not survival times. The influence of distant metastases on prognosis reflected both the site of metastases and the over-all extent of involvement. Bone metastases did not seem to detract from survival times as much as extensive lesions of the breast did when either of these sites of involvement accompanied other metastases. Outlook was so poor for patients with advanced lesions of the breast plus disease in the pleura and lung or in the liver that the early use of the most effective therapy available is encouraged. Endocrine ablation in these patients with no predictive criteria available was as effective as in those patients with recurrent inoperable cancer and favorable selection factors present.

"Residual" mammary carcinoma following simulated partial mastectomy.

Treatment of mammary carcinoma by partial mastectomy rather than by total mastectomy and axillary dissection may diminish the chances of long-term cure by risking incomplete removal of all local carcinoma at the initial operation. This study was undertaken to determine by pathologic examination how often carcinoma might remain in the breast and axilla after partial mastectomy. The operation was simulated in 203 mastectomy specimens after operations for unilateral invasive carcinoma. In so far as could be determined on gross examination, the entire primary lesion was included in the quadrant which was excised in the simulated procedure. Among 100 women with primary lesions less than 2 cm in diameter, 26% had carcinoma in the breast which remained after simulated partial mastectomy. Six percent of them also had axillary node metastases. An additional 30% only had axillary node metastases. When the primary lesion was more than 2 cm in diameter, 38% of patients had carcinoma in the breast after simulated partial mastectomy, of whom 29% also had axillary metastases. After simulated partial mastectomy, carcinoma was found in 80% of breasts from patients with lesions in the subareolar area, in contrast with 25-35% of patients with a primary carcinoma in one of the four quadrants. None of the 9 patients with medullary and colloid carcinomas that measured under 2 cm had axillary metastases or carcinoma in the breast outside of the primary quadrant. The findings suggested that a familial history of breast carcinoma or a large primary lesion may be associated more often with multifocal disease, but factors such as age at diagnosis, axillary status, and the mammogram report did not have significant predictive value for distinguishing between patients who did or did not have carcinoma in breast tissue after the primary had been removed by a simulated partial mastectomy.