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BACKGROUND Although breast conservation therapy (BCT) is standard for breast cancer treatment, patients with tumors measuring >5 cm have been excluded from clinical trials. Nevertheless, only a few small retrospective series to date have compared BCT with mastectomy for tumors measuring >5 cm. The current study was performed to determine whether survival is equivalent for BCT versus mastectomy using a large national data set. METHODS Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked cases were identified for patients aged ≥66 years undergoing breast conservation for invasive, noninflammatory, nonmetastatic breast cancer between 1992 and 2009. Propensity score-based adjustment was used to account for demographics and tumor and treatment factors. RESULTS A total of 5685 patients with tumors measuring >5.0 cm underwent breast surgery, with 15.6% receiving BCT. Mean ages of the patients and tumor sizes were similar. Predictors of BCT included neoadjuvant chemotherapy and postoperative radiotherapy use, higher income, breast cancer as a first malignancy, and a higher Charlson Comorbidity Index. Predictors of mastectomy included younger age, nonductal histology, higher grade, numbers of lymph nodes examined and found to be positive, American Joint Committee on Cancer stage III disease, postoperative chemotherapy use, and residential region of the country. Adjusted overall and breast cancer-specific survival were not different between patients treated with BCT and mastectomy (hazard ratio, 0.934; 95% confidence interval, 0.791-1.103 [P = .419] for overall survival; and subdistribution hazard ratio, 1.042; 95% confidence interval, 0.793-1.369 [P = .769] for breast cancer-specific survival), with each improving over time. The median follow-up was 7.0 years. CONCLUSIONS For Medicare patients with tumors measuring >5 cm, survival is similar between those treated with BCT and mastectomy as for patients with smaller primary tumors. Despite exclusion from randomized trials, BCT may remain an option for patients with larger tumors when deemed clinically and cosmetically amenable to surgical resection. Cancer 2016;122:42–49. © 2015 American Cancer Society.

BACKGROUND The purpose of the current study was to evaluate the locoregional recurrence rate after treatment of patients with operable breast carcinoma with a modification of the Halsted radical mastectomy and the selective use of radiotherapy and to identify risk factors for locoregional recurrence. METHODS Between 1979–1987, 691 consecutive patients underwent mastectomy after a negative biopsy of the axillary apical lymph nodes. The median age of the patients was 59 years (range, 26–89 years). The clinical tumor size was 5 cm in 169 patients; 16 patients had a T4 tumor. Surgery was comprised of a modification of the Halsted radical mastectomy, including at least part of the pectoralis major muscle and the entire pectoralis minor muscle, in 573 patients; 303 patients had positive axillary lymph nodes. Adjuvant radiotherapy to the chest wall and regional lymph nodes was given to 74 patients, whereas an additional 414 patients underwent irradiation to the internal mammary and medial supraclavicular lymph nodes. The median follow-up was 91 months. RESULTS The actuarial overall survival rate was 82% at 5 years and 63% at 10 years. The 10-year chest wall and regional lymph node control rates, including patients with prior distant failures, were 95% and 94%, respectively. The only two significant prognostic factors for locoregional recurrence on multivariate analysis were lymph node status and pathologic tumor size. CONCLUSIONS Excellent locoregional control can be achieved with a modified technique of radical mastectomy in patients with negative apical biopsy and the selective use of comprehensive radiotherapy. These results may serve as a reference outcome for comparison with other locoregional treatment strategies. Cancer 1999;85:1773–81. © 1999 American Cancer Society.

BACKGROUND The National Cancer Data Base (NCDB) is an information resource and program evaluation tool of the American College of Surgeons Commission on Cancer and the American Cancer Society that uses a hospital-based cancer reporting system. The Surveillance, Epidemiology, and End Results (SEER) program is a population-based registry program of the National Cancer Institute. The purpose of this investigation was to compare the aggregate NCDB data for selected cancer types from a given year with comparable SEER data. METHODS SEER data from 1992 on 18,322 breast, 13,427 colorectal, 15,276 lung, and 21,501 prostate cancers were compared with NCDB data on 96,323 breast, 69,456 colorectal, 108,702 lung, and 107,690 prostate cancers. RESULTS Similar levels of data completeness were observed. The NCDB data tended to contain less complete information about the Spanish or Hispanic ethnicity of patients. Tumor grade data tended to be incomplete in both series. Stage information about lung and prostate cancer was more often missing in SEER data. Patient age, race, and gender in NCDB data differed little from corresponding SEER data, except that SEER data reported a greater proportion of patients in the "other" race category that included Asian-Americans and American Indians. Tumor laterality, anatomic site, tumor grade, and types of surgical treatment were similar in the NCDB and SEER data. Radical mastectomy was performed in 49.4% of SEER breast cancer cases compared with 49.2% of NCDB cases. Cancer-directed surgery was observed less often among SEER prostate cancer cases than among NCDB cases. The NCDB data also indicated greater use of radiation therapy than the SEER data for the four types of cancer reviewed. CONCLUSIONS The 1992 NCDB data, in aggregate, described patient and disease treatment characteristics and patterns that differed only marginally from those described in the SEER data from the same year. Cancer 1997; 79:2052-61. © 1997 American Cancer Society.

BACKGROUND This study addresses the controversial prognostic and therapeutic aspects of phyllodes tumor of the breast. METHODS Records of 170 women with phyllodes tumor of the breast were reviewed. On the basis of the criteria proposed by Azzopardi and Salvadori et al., including estimation of tumor margin, growth of the connective tissue component, mitoses, and cellular atypia, the entire series was divided into three histotypes of phyllodes tumor, i.e., benign (92 cases, 54.1%), borderline (19 cases, 11.2%), and malignant (59 cases, 34.7%). Ninety-eight patients (57.6%) were treated by wide local excision (79 benign, 15 borderline, and 4 malignant), 43 (25.3%) by simple mastectomy (13 benign, 4 borderline, and 26 malignant), and 29 (17.1%) by radical mastectomy (all malignant). RESULTS Of the 170 treated patients, 141 (82.9%) survived 5 years without evidence of disease. In the Cox multivariate analysis the histotype of the tumor was the only independent prognostic factor: 5-year NED survival was observed in 95.7% of the patients with benign phyllodes tumor, 73.7% with borderline phyllodes tumor, and 66.1% with malignant phyllodes tumor. After a wide local excision 98.7% of the patients with benign tumor, and 80% with borderline tumor, were cured. Local recurrence was found in 14 patients (8.2%) (4 benign, 3 borderline, and 7 malignant); 10 of these underwent reoperation (7 wide local excision, 3 radical mastectomy) and survived 5 years NED. CONCLUSIONS The histotype of phyllodes tumor (benign, borderline, and malignant), assesed on the basis of the criteria proposed by Azzopardi and Salvadori et al., was the only prognostic factor in our group of patients. Based on the data from literature and our own observations, we observed that a wide local excision, with an adequate margin of normal breast tissue, is the preferred initial therapy for phyllodes tumor of the breast. Cancer 1996;77:910-6.

The current management of carcinoma of the breast is very different than it was a relatively few years ago. The improvements in care have been introduced into practice as a result of clinical trials. From the nonrandomized but controlled clinical trial of radical mastectomy by William S. Halsted demonstrating that locoregional control could be dramatically improved, trials have become considerably more sophisticated in both design and analysis. Randomized clinical trials of breast conservation therapy were begun in Milan by Dr. Veronesi. Trials by the National Surgical Adjuvant Breast and Bowel Program headed by Dr. Bernard Fisher have, with other trials, defined the benefits and techniques of this less morbid treatment approach. Improvements in survival have also emerged from randomized clinical trials of adjuvant systemic therapy. Although these improvements are significant, they do not eliminate the risk of death from breast cancer. Much remains to be answered in the clinical management of breast cancer. Clinical trials will assess new developments and introduce improvements to clinical practice. Funding for research in breast cancer must support basic investigation into the biology of the disease process, new approaches to control disease, and clinical trials to test therapeutic principles and techniques.

Background. Late menarche, early menopause, high parity, and early first birth decrease the risk of development of breast cancer. The influence of these factors on the survival of breast cancer patients has not been explained. Methods. A group of 1885 patients with operable breast cancer was studied retrospectively. A univariate analysis was used to calculate 10-year overall survival (OS) and disease free survival (DFS) in relation to age, menopausal status, age at menarche and menopause, and number of pregnancies and deliveries. A multivariate analysis (Cox model) was performed in which classic prognostic factors (tumor size and grade, lymph node involvement) were included in addition to reproductive factors. Results. Univariate analysis demonstrated better prognosis in patients who had never been pregnant compared with those who had (OS, 62% vs. 54%, respectively; P = 0.01; DFS, 53% vs. 44%, respectively; P = 0.005) and in nulliparous compared with parous patients (OS, 62% vs. 53%, respectively; P = 0.006; DFS, 52% vs. 44%, respectively; P = 0.004). Survival rates decreased with the number of pregnancies and deliveries. Patients with late menarche had worse survival then those whose first menstruation occurred before the age of 16 years (DFS, 47% vs. 41%, respectively; P = 0.04). By multivariate analysis, parity remained an independent prognostic indicator in addition to classic highly significant prognostic factors (nodal involvement, tumor grade and size). Conclusions. Results suggest that reproductive factors known to decrease the risk of breast cancer development have an adverse effect on prognosis.

Lumpectomy and irradiation is an increasingly popular treatment option for women with breast cancer. Currently, modified radical mastectomy is selected about as often. Most women choosing to have a mastectomy desire reconstruction to improve the cosmetic result; this procedure can be done immediately or at a later time. If immediate reconstruction using a plastic implant is selected, an expander can be used if the skin cover is inadequate. A myocutaneous flap can be used either immediately or later and whether sufficient skin is available. The trans rectus abdominal myocutaneous (TRAM) flap is increasingly popular because a large amount of tissue can be transferred and the cosmetic blemish from tissue transfer is preferable on the lower abdomen than elsewhere. Treatment costs are of some importance. The cheapest procedure is the modified radical mastectomy; lumpectomy with iridium implant is the most expensive, and the other treatments fall in between.

When Cancer began publishing in 1948, 1 of the first articles to appear was a review of sex hormones and advanced carcinoma of the breast. Because little was then known about the biology of breast cancer, standard treatment was characterized by radical and disfiguring surgery, often with only a limited effect on long-term outcomes. Several pivotal developments in the ensuing 60 years changed this picture dramatically. The large tumors that were common at initial presentation in 1948 became increasingly uncommon with the growing use of screening mammography. It was soon suggested that these smaller tumors could be successfully treated with more conservative surgery, especially with the addition of multidrug chemotherapy and hormonal therapy as adjuvant treatments. These revolutionary developments, which have allowed many women to remain free of disease for extended periods of time, were chronicled in landmark papers that appeared in Cancer: the first clinical trial to determine whether screening mammography would improve outcomes, the early small trials comparing less invasive surgery with Halsted's radical mastectomy, the initial National Surgical Adjuvant Breast Project trial testing the efficacy of triethylenethiophosphoramide in combination with radical surgery, and the first antiestrogen trials. These articles are extraordinary not only for breaking new ground in their respective technical areas, but also for the keen insights shown by the authors into what would become important in the future.

BACKGROUND In the current study, the authors compared the incidence of subsequent primary lung carcinoma in patients with breast carcinoma who received radiotherapy as part of their treatment and in those patients who did not. The patients were participants in two large National Surgical Adjuvant Breast and Bowel Project (NSABP) breast carcinoma trials, B-04 and B-06, which prospectively randomized women to either undergo surgery alone or to undergo surgery and postoperative radiotherapy. METHODS The NSABP trial B-04 (1971–1974) randomized patients to undergo radical mastectomy versus total (simple) mastectomy and radiotherapy to the chest wall, axilla, and supraclavicular and internal mammary lymph node areas. For patients with a clinically uninvolved axilla, there was a third randomization arm: total mastectomy without radiotherapy. The B-06 trial (1976–1984) randomized patients between those undergoing total mastectomy versus lumpectomy versus those undergoing lumpectomy and breast irradiation, with all patients undergoing an axillary lymph node dissection. The records of all patients who developed a recurrence in the lung or a new primary lung tumor were reviewed to determine the incidence and laterality of confirmed and probable primary lung carcinoma. RESULTS For the 1665 evaluable patients on the NSABP B-04 trial (mean follow-up of 21.4 years), there was a total of 23 subsequent confirmed and probable ipsilateral or contralateral primary lung carcinomas. In those patients who had received comprehensive postmastectomy radiotherapy, there was a statistically significant increase in the incidence of these new primary tumors (P = 0.029). With regard to the development of confirmed new primary ipsilateral lung carcinoma alone, the incidence was statistically significantly increased (P = 0.013) in those patients who had received radiotherapy as part of their treatment, and when confirmed and probable ipsilateral lung carcinomas were analyzed, there was a strong trend toward a statistically significant increase in those patients who had received radiotherapy (P = 0.066). For the 1850 evaluable patients on the NSABP trial B-06 (mean follow-up of 19.0 years), there was a total of 30 second primary lung carcinomas but no increase in either ipsilateral or contralateral primary tumors of the lung in those patients who had received radiotherapy. CONCLUSIONS Extensive postmastectomy irradiation of the chest wall and regional lymphatic node areas, with consequent exposure of a greater volume of lung to higher doses as administered in the NSABP B-04 trial compared with postlumpectomy breast irradiation in the NSABP B-06 trial, was associated with an increased incidence of subsequent primary lung tumors, both ipsilateral and contralateral. Cancer 2003;98:1362–8. © 2003 American Cancer Society. DOI 10.1002/cncr.11655

It comes as no surprise that radiation at high doses can cause lung cancer. Survivors of the atomic bomb explosions in patients given radiotherapy for ankylosing spondylitis3 or and underground miners exposed to radon' all have been reported to be at increased risk of lung cancer. There is growing evidence that adjuvant radiotherapy for breast cancer after radical mastectomy, a common treatment practice in previous decades, but less so today, also is associated with an increased risk of lung cancer 10 or more years later.'"" For medically exposed populations, it is important to understand the magnitude of possible treatment risks, the associated benefits, and the relevance to current practice. The joint effects of radiation and other environmental exposures, most notably cigarette smoking, also await clarification and are of scientific interest for what they may imply atout the mechanisms of lung carcinogenesis. The paper by Neugut and colleagues in this issueI2 addresses the combined effects of radiation therapy and smoking, with a view toward the possible clinical implications. The authors report a 3-fold relative risk (RR) associated with radiotherapy for breast cancer among 10-year survivors, a 14-fold RR associated with cigarette smoking, and a 33-fold risk among irradiated smokers. Each of these associations was more pronounced for lung cancers occurring in the lung on the same side of the body as the breast cancer (ipsilateral) than for those occurring on the opposite (contralateral) and less heavily irradiated side. The authors suggest that radiotherapy and smoking act multiplicatively and that smokers represent a subgroup in which the absolute risks associated with radiotherapy are much greater than for nonsmokers, large enough, perhaps, to be an important consideration in the design of breast cancer treatment for smokers.

BACKGROUND With the move away from classical radical mastectomy to ever more skin-sparing procedures, there has been an ongoing discussion about how much skin and subcutaneous tissue should be resected to perform an adequate mastectomy while leaving viable skin flaps. One of the common recommendations is to dissect just superficial to the superficial layer (SL) of the superficial fascia of the breast. This, in turn, has revived the old, unsolved controversy about the existence or absence of the SL, a fascia that reportedly encloses the mammary gland ventrally. In skin-sparing mastectomies (SSM), which combine tumor resection with immediate breast reconstruction, the ideal would be to create skin flaps that are thin enough to remove all breast tissue but at the same time are thick enough to preserve flap circulation. The feasibility of meeting these two goals simultaneously and the possible role and relevance of the SL as a guide to dissection in SSM was examined in this study. METHODS Sixty-two breast resection specimens from 31 women who underwent breast reduction were examined histologically to determine whether the SL was present, whether breast tissue could be detected within or beyond this SL, the measured distance between the caudal border of the dermis and the SL or the breast tissue, and whether the thickness of the subcutaneous fat layer was correlated with the patients' physical data, such as body weight or body mass index (BMI). RESULTS The SL was absent in 44% of resection specimens. When the SL was present, 42% of specimens contained several islands of breast tissue within the SL. No breast tissue was found beyond the SL. The minimal distance between the SL and the dermis varied from 0.2 mm to 4.0 mm; the minimal distance between the breast tissue and the dermis was 0.4 mm. In 50% of specimens, the minimal distance between the dermis and the SL or breast tissue was < 1.1 mm. A distance of ≥ 5 mm was encountered in only 17% of specimens, and a distance of ≥ 10 mm was encountered in only 5% of specimens. No significant correlation between the right and left breast was found with any of the parameters examined. A weak negative correlation was seen between the BMI and the mean thickness of the subcutaneous fat (P = 0.049; correlation coefficient [r] = −0.39; Spearman rank correlation). CONCLUSIONS Histologic evaluation revealed that the SL is not present in all breasts and, thus, cannot serve as a reliable plane of dissection. Furthermore, if the SL is present microscopically, then it often is too thin and delicate to be detectable macroscopically. Finally, even if the SL is present and visible macroscopically, the distance to the overlying skin is so small in the majority of patients that a dissection superficial to the SL would not leave viable skin flaps in skin-sparing mastectomies. Cancer 2002;94:1619–25. © 2002 American Cancer Society. DOI 10.1002/cncr.10429

Medical personnel should be aware that the Reach to Recovery program has gone from one visit to a radical mastectomy surgery patient to a multifaceted program. Reach to Recovery volunteers have been trained to make lumpectomy, mastectomy, reconstruction, and recurrence visits. They make visits not only in the hospital but at alternative locations (home, physician's office, library, coffee shop). Older women have the same needs as all women-getting back to normal, feeling good about themselves, and their sexuality. Older woman should not be ignored because of their age. Volunteers who visit patients are matched to a patient according to the type of surgery performed and the patient's age; older volunteers visit older patients

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.

Sixty-four women with Stage II breast cancer who had Sr85 bone scans at the time of radical mastectomy were followed for 8 years in a prospective study. Those women with positive scans had a slight, but statistically significant, increased incidence of metastic disease, particularly for metastases to bone.However, 40% of those women with positive bone scans and negative roentgenograms survived 8 years without evidence of any metastatic disease. Therefore, it has not been shown at this time that bone scans should be obtained in order to exclude bone metastasis before regional therapy for breast cancer is instituted. Also, a significant percentage of women with negative bone scans developed both bone and soft tissue metastases. As many as 30% of asymptomatic women with a history of breast cancer and positive bone scans and negative bone roentgenograms may still harbor disease in bone after 8 years.

Considerations for surgical treatment of locoregional recurrences of breast cancer are particularly relevant at a time when many primary breast malignancies are being treated in a more conservative manner. The past experience with local recurrence after radical mastectomy was dismal: every patient with recurrence eventually developed systemic disease. Over 80% of such patients died within 2 years. The observations after local recurrence in patients with modified radical mastectomy are generally the same, although those with better prognostic lesions may have a marked delay in mortality. For patients with partial mastectomy and radiation, there are data which suggest that subsequent mastectomy for "in breast" recurrence may salvage approximately 50% of women and achieve long-term freedom from disease. This is a crucial question which will require more patients and time for confirmation. The author reviews patterns of locoregional recurrence after primary treatment of breast cancer, presents a plan for workup of such patients, and describes prognostic factors. The various treatment options, with their results, are discussed, and their dependency on the initial therapy is stressed. For patients with advanced Stage III primary breast cancer (T4 or N2, N3 lesions) and inflammatory carcinoma, a multimodal approach is proposed, with systemic multidrug chemotherapy as the initial treatment. The interlocking roles of surgical resection of the breast and radiation therapy must be considered, depending on the response to chemotherapy. Algorithms for therapy have been constructed to demonstrate the options.

The relevance of cell kinetics of the primary tumor as a marker of biologic aggressivity was verified on a series of 258 patients with operable breast cancer without nodal and distant metastases, who underwent radical mastectomy without any other treatment until relapse. The cell proliferative rate, evaluated in vitro on fresh tumor material and expressed as 3H-thymidine labeling index, was found to be an important discriminant of metastatic potential. Patients with slowly proliferating tumors showed a higher probability of 6-year relapse-free survival in comparison to those with fast-proliferating tumors (80.5% versus 59.6%, P = 0.00004). This finding was true for premenopausal and paramenopausal (P = 0.00005) as well as for postmenopausal patients (P = 0.01). The kinetic variable was also a discriminant of 6-year survival for the overall series (P = 0.003) and for premenopausal and paramenopausal patients (P = 0.003) regardless of the type of treatment after relapse. These findings show the relevance of the kinetic variable as an important prognostic marker in breast cancer.

A statistical assessment of several "randomized" clinical trials was carried out and the following conclusions were noted. 1. There is no statistically significant evidence that radiation to the peripheral lymphatics and/or chest wall following radical mastectomy affects survival. 2. There is significant evidence that postoperative irradiation to the peripheral lymphatics and/or chest wall does decrease local recurrence rate. 3. There is reliable evidence that the treatment of local recurrence, once it develops, is successful in only 50% of the cases. 4. There is evidence that radiation plus simple mastectomy is as effective in the treatment of breast cancer as radical mastectomy alone. It is our considered opinion that radiation remains a useful adjuvant and complementary agent in the treatment of breast cancer, is not harmful vis a vis survival and should be used when and where indicated.

Eleven new cases of adenoid cystic carcinoma of the breast are added to the 95 previously reported. They were studied for their biological behavior, and an attempt was made to correlate histologic features with prognosis. A comparison was made with analogous tumors in extramammary sites, and possible relationship with carcinoid tumors of the breast explored. The patients in the study followed a biological course very similar to that described by previous studies, i.e., slow progression, local recurrence if inadequately resected, and absence of lymph node metastases. Only one patient developed distant metastases after an interval of ten years following radical mastectomy. If the diagnosis of adenoid cystic carcinoma is reserved for those lesions displaying the distinctive appearance and typical epithelial-stromal relationships which have been described, the authors feel that simple mastectomy with careful follow-up surveillance is the treatment of choice.

The combination of conservation surgery and radiation therapy for early breast cancer is gaining acceptance as an alternative to radical mastectomy. This article reviews the results of randomized trials showing that there is no advantage to a radical mastectomy in patients with early breast cancer. In addition, the article will review multiple reports concerning the local and regional tumor control and survival of patients treated with conservation surgery and irradiation as well as a comparison of 1073 patients with TIS T1 T2 N0 N1 breast cancer treated at University of Texas (UT) M. D. Anderson Hospital between 1955 and 1980, of whom 345 were treated with conservation surgery and irradiation and 728 were treated with radical or modified radical mastectomy alone. The locoregional recurrence in the patients treated with an intact breast is 4.9%, and 5.6% in patients treated with radical or modified radical mastectomy. There is no significant difference in the 10-year disease-free survival rates between the two groups of patients. In addition, a comparison of 2467 patients with Stage I and Stage II breast cancer treated at the UT M. D. Anderson Hospital shows no significant difference in the incidence of consecutive second breast carcinoma as a result of the use of radiation therapy in the treatment of the first breast cancer.

A survey of controlled randomized trials of orthodox therapy directed to the breast and axillary nodes has indicated that 1) if radical mastectomy is performed, postoperative radiotherapy gives no advantage over a watching policy and 2) if postoperative radical radiotherapy is given, there is no need for other than a simple mastectomy.33 A large multicenter trial is also indicating that simple mastectomy alone with reservation of radiotherapy for treating local recurrent disease is safe initial treatment.30 These results refer to survival; postoperative radiotherapy does reduce the incidence of local recurrence but this apparently can be equally well treated when it occurs. Local excision of the tumor, followed by radiotherapy, has been reported to give inferior results to a radical approach in Stage II tumors.2 Recognition that all these methods of local treatment fail to cure the majority of patients has emphasized the need to define the extent of the disease and to apply treatment according to that extent. We have studied a policy of selective local therapy based on this principal in which total mastectomy is combined with biopsy of the pectoral lymph nodes and further treatment by radiotherapy given only if these nodes are involved by tumor.16,17 This policy has been compared with a standard radical approach and is giving similar results.31 In our current Edinburgh trials, pectoral node biopsy is also used to select patients for inclusion in trials of systemic therapy.29a

The thymidine labeling index (TLI) was measured in vitro in 278 primary breast carcinomas. In 227 operable women treated by radical mastectomy, TLI's below the median of 4.55% carried a probability of relapse of 20% at four years, in contrast to 52% for TLI's above the median (P = 0.0001). The probability of relapse was significantly related to the TLI independent of TNM pathologic stage, axillary lymph nodal status alone, estrogen receptor (ER) content, or menopausal status. The abilities of the TLI and nodal status to predict early relapse were equally strong and independent, whereas other variables tested had less or no independent predictive capacity. The predictive value of the ER content depended largely on its relationship to the TLI, and ER was related to the probability of relapse in the below median TLI group only. The TLI can select a subgroup of node-negative patients with a relapse-expectancy of approximately 50% at four years.

Internal mammary lymph node biopsies were performed during radical mastectomy in 113 cases of invasive carcinoma of the breast. Metastases were found in 25 cases, 22% of the total. One hundred five of the cases received no further treatment unless cancer recurred and were observed for an average of 13.6 years. Local recurrence and 10-year mortality were significantly increased in the presence of internal mammary metastases, but it could not be demonstrated that the latter increased chest wall recurrence or decreased survival independently of axillary lymph node involvement. The survival of five patients with internal mammary metastases who were treated with postoperative irradiation or castration was not superior to that of 20 patients with untreated metastases. It was concluded that internal mammary metastases usually reflect generalized tumor spread and that local therapy directed at these nodes has a negligible influence upon cure of the disease. In that they reflect a poor prognosis, metastases at this site would justify systemic adjuvant chemotherapy.

Modified radical mastectomy was performed in 162 patients with minimal breast cancer between 1953 and 1972 (JAU). The majority of lesions were small infiltrating cancers (52), non-infiltrating duct cancer (37), lobular carcinoma in situ (49), Paget's disease with non-infiltrating cancer (12), and also a small group of miscellaneous low-grade cancers (7), and malignant cystosarcoma phyllodes (5). Major indications for surgery were the presence of a mass, nipple ulceration, positive mammograms, and the discovery of an occult cancer on contralateral biopsy. Mammography was accurate in 60% of patients with minimal breast cancer. Contralateral biopsy proved to be a very sensitive diagnostic technique, and was positive in 35 patients, most of whom were negative by clinical examination and mammography. Residual cancer was found in the mastectomy specimens in 52% after generous excisional biopsies. Sixteen percent of patients with minimal infiltrating cancer and clinically negative axillae had micrometastases (2mm or less) in axillary nodes. The crude survival rate free of disease was 93 of 95 patients (98%) at 5 years, and 42 of 44 patients (95%) at 10 years. There were no local recurrences. No postoperative radiation was used on these patients. Modified radical mastectomy is recommended as the ideal treatment for minimal breast cancer as it yields excellent long term salvage, complete local control, and is more acceptable cosmetically than the classical radical mastectomy. It is to be preferred over extended lumpectomy (tylectomy) with radiation therapy since it avoids the potential long-term carcinogenic effects of ionizing radiation. The excellent results obtained by adequate treatment of minimal breast cancers attest to the need for reliable mass screening techniques to detect occult, asymptomatic breast cancer, and for the availability of these techniques to the public at large.

Primary radiation therapy for early breast cancer is a combination of limited breast surgery for the removal of gross disease, and moderate doses of radiation for the control of residual subclinical disease. The results from retrospective studies using primary radiation therapy indicate that high levels of local tumor control with good cosmetic results can be achieved. Preliminary results from a prospective randomized clinical trial indicate that radical mastectomy and primary radiation therapy result in equivalent survival rates. Primary radiation therapy is a reasonable alternative to mastectomy when adequate surgical and radiotherapeutic expertise is available to deliver this treatment.

Between 1971 and 1974, 1,665 women with primary operable breast cancer were entered into a prospective randomized clinical trial (NSABP Protocol No. B-04) in order to compare the worth of radical mastectomy with alternative treatments. Six-hundred forty-six of the women, 352 clinically nodenegative and 294 node-positive, were randomized so that they were to have been treated with total mastectomy and postoperative radiation. Due to a meticulous comprehensive program of radiation monitoring involving close cooperation between the NSABP Headquarters, the NSABP Radiation Monitoring Committee, the Radiological Physics Center at M. D. Anderson Cancer Center and participating institutions, it has been possible to determine protocol compliance of the radiation administered and to correlate any variation of radiation employed with treatment outcome. At the onset of the study and prior to any evaluation of treatment results, the Radiation Monitoring Committee defined minor variations from the protocol which were acceptable and those variations which were more major and unacceptable. While it was found that 53% of the 543 evaluable patients had been treated by radiation having some degree of variation from the protocol, it was ascertained that 77% of the 2.172 irradiated fields of those patients (82% in clinically node-negative and 71% in clinically node-positive patients) received radiation per protocol. Only 6.7% of all sites were the recipients of a major (unacceptabel) variation in radiation. Analysis of data demonstrated that there was a remarkable similarity in the incidence and rate of treatment failure (TF) or mortality between patients having some radiation variation, regardless of its degree or extent and those who were treated with no protocol variation. Results were similar when comparisons were made taking into consideration either the degree (minor or major low) or the extent (one or more than one field) of the radiation variation. A substantial number of clinically positive axillary node patients received only the radiation to the axillary field intended for those with clinically negative nodes, i.e., they failed to receive the specified radiation boost. Despite that deviation, there was no difference in TF or survival from those receiving the prescribed treatment. Moreover, findings were not different when the axilla was the only site of radiation deviation or there were deviations to other fields as well. Of singular importance was an inability to associate the localregional location of a recurrence with a low-dose radiation deviation at the site. Almost all recurrences in clinically node-negative patients were at sites treated per protocol. In positive-node patients, supraclavicular and chest wall recurrences occurred in patients having acceptable radiation to those sites and axillary recurrences were equivalent in patients treated with or without deviations at that site. The findings from these investigations are not presented in order to indicate that the quality and quantity of radiation may be unimportant. They have been obtained under careful monitoring and the variations are within a relatively narrow range. Consequently, more general extrapolations from these must be made with circumspection. The observations do suggest, however, that there is some acceptable leeway in the use of radiation, at least for treatment of the extent of disease present in patients in this study. Moreover, they refute any consideration that the failure to demonstrate a significant advantage following the use of postoperative radiation in Protocol No. B-04 could be related to the variation and inadequacy of radiation employed in a proportion of the patients. They tend to substantiate the contention that factors other than the type of operative procedure employed or the precision of administration of radiation are important in determining the survival of women with breast cancer. Finally, the mechanism whereby the radiation employed was quality controlled serves as a model for the mandatory monitoring of all modalities of therapy in cooperative clinical trials. Such monitoring, by providing more credible dat, will favorably affect the management of cancer patients. Cancer 46:1–13, 1980.

The combination of conservation surgery and radiation therapy for favorable breast cancer is gaining acceptance as an alternative to radical mastectomy. Presented here is a review of the local and regional tumor control and survival results of several authors, as well as a comparison of 1073 patients with clinically favorable breast cancer treated at the University of Texas M. D. Anderson Hospital between 1955 and 1980, 345 of whom have been treated with conservation surgery and irradiation and 728 of whom have been treated with radical or modified radical mastectomy alone. The locoregional recurrence in the patients treated with an intact breast is 4.9%, and 5.6% in patients treated with radical or modified radical mastectomy; there is no significant difference in the 10-year disease-free survival rates between the two groups. A detailed analysis of the location and timing of recurrences and the incidence of contralateral breast cancer is presented.

The combination of radiation therapy (RT) and conservation surgery is appropriate treatment for Stage I and II breast cancer patients, and is equivalent to radical mastectomy in overall survival and recurrence free survival. Moreover, RT and conservation surgery has the advantage over radical surgery of breast preservation (and subsequent psychological advantage). Inherent in the preservation of the breast is the concept of cosmesis. This implies that the treated breast is not retracted or deformed by the surgery and radiation. Current studies indicate that there is an increase in complications and less satisfactory cosmetic effect on patients receiving chemotherapy in conjunction with conservation surgery and RT, but no effect on survival. This raises the question of which patients should receive chemotherapy and what type of chemotherapy should be used. It also raises the question of the initiation timing and dosage of chemotherapy.

Eighty-one patients with cancer of the male breast were studied. The majority (79) presented with a mass in the breast and in 8 patients the tumor was found by chance. Two patients presented with serosanguinous discharge. Average duration of symptoms was 11.9 months. Thirty patients had Stage I, 25 had Stage II, 16 had Stage III, and 8 had Stage IV disease. Fifty-three patients had simple mastectomy, nine had lumpectomy, six had radical mastectomy, and five had biopsy only. Eight had no local surgery. Overall 5- and 10-year survival allowing for all causes of death was 38% and 17%, respectively. Cox's (1972) proportional hazard regression model was used to assess the contribution of various factors to survival. Age at presentation, postoperative hormone therapy, postoperative radiotherapy, site of the primary tumor within the breast, and type of local surgery did not contribute to survival. Only the stage of disease contributed to survival and did so in the expected direction.

At present, through public awareness and the use of improved diagnostic aids, increasing numbers of patients are being seen with localized "minimal" breast cancer. In our own experience, the average measured size of the primary tumor has diminished from 3.2 cm in 1955 to 2 cm in 1974. Although the incidence of axillary node metastases has diminished only from about 50% to 42% during this interval, the extent of involvement and the distribution of nodal disease has improved markedly with a marked decrease in apical node involvement. Mammography has been responsible for the detection of more than 50% of our "minimal" breast cancers. This improved patient material presents a great potential for improved control of this disease. In planning the choice of surgery for primary breast cancer, its multicentric origin, and regional nodal spread to axillary and internal mammary nodal areas must be considered. There is no single ideal operation for all breast cancers. The scope of surgery should be correlated with the clinical and pathologic extent of disease in the individual patient with the aim of removing all disease present while preserving appearance and function-the main goal being removal of disease. We have utilized three operative procedures: total mastectomy with axillary dissection, radical mastectomy, and extended radical mastectomy. With this approach a 10-year survival rate of 61% with a local recurrence rate of 7.7% has been attained in a group of 565 patients with 40% axillary node involvement. The best salvage obtained in patients with "minimal" breast cancers-noninfiltrating cancers and infiltrating cancers under 1 cm in diameter with clinically negative axillae-was 95% survival at 10 years following modified radical mastectomy (total mastectomy with axillary dissection). When disease has extended to the axillary nodes the more extensive procedures have proved more effective in achieving long term control-54% 10 year survival in patients with axillary node metastases treated by the extended radical mastectomy. An increasing number of patients are being seen who can be treated adequately by less than a radical mastectomy. Careful clinical judgment and close liason with a competent pathologist must be combined in selecting the proper operative procedure for each individual patient. Statistics concerning therapeutic effects based on current material, unless they are based on accurate data covering extent of disease, cannot be compared with previous data because of the improved patient material now being encountered. Adjuvant multiple chemotherapy appears promising as a supplement to surgical treatment of breast cancer. However, it should not be used to replace or minimize the role of primary surgery, but should be combined with the optimum procedure for each individual patient.

There is no ideal single operation for breast cancer. In planning the choice of surgery for breast cancer, one must be aware of its multicentric origin, and of the regional spread from the breast to the axillary and internal mammary lymph nodes. The scope of the surgical attack should be correlated with the clinical pathologic extent of disease in the individual patient with the aim of removing all disease present, while preserving appearance and function to the utmost. The main goal remains removal of all disease from the breast and its regional nodes. Three distinct operative procedures have been utilized--modified radical mastectomy--total mastectomy with axillary dissection, radical mastectomy, and extended radical mastectomy. In all instances, the appropriate operation is applied to the individual, with the concept of removing most efficiently all disease present in the breast and regional nodes. With this plan of therapy, a 10 year survival rate of 61% with a local recurrence rat of 7.7% has been attained in a group of 565 patients with 40% axillary node involvement. These data are crude and uncorrected for age, intercurrent disease and for those lost to follow-up. The best salvage has been attained in the so-called "minimal" breast cancers--95% well 10 years following modified radical mastectomy. The extended radical mastectomy has been superior to the radical mastectomy when axillary node disease is present. In the more complete operation, 54% 10 year survival has been attained in patients with axillary node metastases, compared with only 33% attained in those treated by the conventional radical mastectomy. Adjuvant radiation therapy is applied to the adjacent regional nodes, when indicated. Adjuvant multi-chemotherapy is in its infancy and still to be evaluated. It should be used as a supplement to adequate primary surgical treatment, and should not be used as a crutch for inadequate primary surgery.

The approach to primary operable, or potentially curable breast cancer is a controversial field of oncology and is subject to a number of ongoing clinical experiments in many centers. This report discusses the recommended treatment for patients with this disease who are evaluated at the Breast Service of Memorial Sloan-Kettering Cancer Center. The most widely practiced treatment is modified radical mastectomy, with radical mastectomy reserved for patients having more advanced lesions. Modified radical mastectomy is defined as total mastectomy plus axillary lymph node dissection either with preservation of the pectoralis minor muscle or its removal. The latter allows a more thorough axillary dissection and is preferred for patients with invasive carcinomas. In either case, axillary node sampling is not advocated and will miss a significant percentage of axillary metastases. In patients with negative axillary lymph nodes, who are not candidates for adjuvant systemic therapy, breast reconstruction is possible within a few months of mastectomy. For patients with involved axillary nodes, trials of adjuvant chemotherapy (perhaps with antiestrogen therapy for estrogen-receptor positive primary tumors) seem to offer the best hope for improved survival. With available follow-up of such trials to date, there seems little doubt that at a minimum, such treatment prolongs disease-free interval. The role of adjuvant radiation therapy is more controversial, and the difficulty in combining this with chemotherapy is apparent.

A prospective study of factors that might be helpful in predicting recurrence of breast cancer during the 2 years after radical mastectomy has been completed in 381 women by the Cooperative Breast Cancer Group (National Cancer Institute). Identification of clinical factors which might be associated with such recurrence has been achieved. A multivariate analysis of the data was oriented toward the identification of clinical factors other than lymph node status that might be simultaneously used to predict recurrence because of the current trend of cancer therapy toward more limited surgery. Degree of differentiation of the tumor, blood vessel invasion, patient age and tumor size were identified as important predictors of recurrence for premenopausal patients and tumor size was identified as important for postmenopausal patients. The addition of axillary lymph node status to these factors, however, made a significant improvement in the prediction equation for both pre- and postmenopausal patients. Studies of this type are of particular value to understand further the biology of breast cancer which is necessary to develop rational primary and adjuvant treatment strategies. Cancer 42:2809–2826, 1978.

Thirty-six pathologic and six clinical characteristics observed in 581 patients enrolled in protocol no. 4 of the National Surgical Adjuvant Breast Project were treated by radical mastectomy and were correlated with five-year treatment failure. The cases were initially stratified according to pathologic nodal status, the most important discriminant in breast cancer. The presence of tumor necrosis, poor tumor differentiation (histologic grade 3) and a tumor size > 4 cm were found by multivariate analyses to influence treatment failure in patients without nodal metastases. Prognosis was usually worse in individuals whose tumors exhibited all of these features than in those in whom only one or two could be detected. Although the sample size was small, life-table analysis also disclosed a highly significant relationship between treatment failure and a germinal center predominance pattern in regional nodes in this subset of patients. Except for this latter, these same discriminants were similarly noted to affect treatment failure in those patients with four or more nodal metastases but not those with only 1--3 positive nodes. A possible explanation for this inconsistency among nodal categories is discussed. Nevertheless, it is concluded that these rather easily measured pathologic parameters represent important discriminants for the prognosis and the design of treatment schemes and subsequent protocols for patients with breast cancer, particularly those without regional nodal metastasis. The findings amplify the importance of intrinsic tumor characteristics as well as possibly host factors in accounting for the clinical behavior of patients with breast cancer.

Two hundred thirty-seven patients with cancer of the breast treated with radical mastectomy were reviewed. Coefficients of correlation between patient's and doctor's delay vs. survival were not significant at p smaller than 0.05. No significant relationship between delay and time of recurrence was found.

The report describes a clinical trial on conservative surgery in progress at the National Cancer Institute of Milan, Italy. The randomized clinical trial compares radical mastectomy with a more conservative procedure consisting of mammary resection plus axillary dissection plus radiotherapy. The resection comprises an entire quadrant of the breast together with the overlying skin and the corresponding portion of the fascial sheet of the pectoralis major. The axillary dissection is performed in continuity with the resected breast quadrant except in cases with tumors of lower inner quadrants, who need two separate incisions. After surgery the patients receive 6000 rads to the residual breast tissue over five to six weeks, starting 15 days after operation. The cosmetic results are satisfactory in approximately 70% of cases. The trial is limited to cases with tumors less than 2 cm and no palpable axillary nodes (T1N0M0). Patients with histologically positive lymph nodes (N+) are submitted to adjuvant chemotherapy with CMF for one year. From September 1973, to October 1976, 331 cases entered the trial. One hundred sixty were treated with radical mastectomy and 164 with the conservative procedure. Axillary metastases were found in 23% of the radical and in 29% of the conservative surgery group. Four local-regional recurrences have occurred till now, two in each group. Five cases in the radical mastectomy group and one in the conservative group had distant metastases. The clinical trial will collect some 500 cases by the end of 1977 and significant preliminary results are expected to be available from 1978.

This report describes our experience with a technique of modified radical mastectomy involving incision of the lower lateral fibers of the pectoralis major muscle and detachment of the origins of the pectoralis minor muscle. These maneuvers enable sufficient retraction of these muscles to provide excellent axillary exposure while minimizing the danger of traction injury to the neurovascular structures supplying these muscles. The operation has been performed in 20 patients; statistical analysis demonstrates at least as many nodes in these specimens compared to retrospective analysis of nodes recovered from 223 radical mastectomy specimens done during the previous 5 years. The final cosmetic results are superior to those obtained with standard radical mastectomy. These results suggest that this method of modified radical mastectomy should be considered, unless the proximity of the disease to the pectoralis muscles endangers the adequacy of the surgical margins.

This study conducted from 1964-1970 reports on 392 women who had mastectomies and chemotherapy who survived more than 3 years. Chemotherapy involved 3-4 consecutive courses starting with the operation of 20-40 mg iv of thiotepa and then 3 mg/kg every other day until the maximum tolerable dose of 240-280 mg was achieved and 4-6 gm of cyclophosphamide or occasionally 3 mg/kg of Benzotepa every other day. Additional therapy by oopherectomy and testosterone propionate and prednisolone administration was performed. The results suggest that to reduce the number of distant metastases after mastectomy primary breast cancer treatment should include 3-4 subsequent courses of chemotherapy given at 6-8 week intervals in order to affect tumor cell population. This chemotherapy regimen improves the long-tern chances of survival without recurrence (1.5 times). After radical mastectomy chemo- and hormone-therapy in cases of multiple regional mestastases increases the number of survivors without distant mestastases by nearly 2 times compared to the results of operation and irradiation alone (40% and 21.5% respectively). The planned combined treatment was not effective in 10.7% of patients because of persistent leukopenia caused by preoperative telegamma therapy. Chemotherapy caused exacerbation of chronic liver and kidney disease in 4.4% of the patients. Two-thirds of those receiving an incomplete chemotherapy course eventually developed distant mestastases.

This is a resume of a Breast Cancer Survey carried out by the American College of Surgeons in 1978. Four hundred and ninety-eight hospitals in 47 states, Washington, D. C., and Puerto Rico participated, contributing a total of 24,136 female patients with histologically confirmed breast cancer. In these patients, five-year cure rates were 60.5% for clinically localized disease and 33.9% for regional disease. Five-year survival rates were 72.8% for localized disease and 49.1% for regional disease. From the 1960's into the early 1970's, there was a gradual shift away from radical mastectomy towards so-called modified radical mastectomy. In a group of patients treated by either radical or modified mastectomies, the axillary nodal status, size of the tumor, and location of the tumor were examined in relation to the prognosis. In the study of number of metastatic nodes in the axilla, there were reduced cure and survival rates in patients with one or more positive nodes as compared to those with negative axillary nodes. With the increase in the number of positive nodes, there was a continuing associated decline in survival and cure. The clinical size of the tumor also correlated well to the prognosis. With the increase in the size of the tumor, there was a gradual increase in the probability of axillary nodal involvement. However, in the group of patients with tumor size smaller than 1 cm, axillary metastasis occurred in 25%. When the axillary nodes were involved, the cure rate in those patients was not significantly better than the rates for those with larger primary tumors in this study. Tumors located in the medial half of the breast were associated with a slightly lower cure rate than those in the lateral half. Young women under 35 years of age had poorer survival and cure rates, although in women 35–44 years of age, the five-year results were comparable to the older group of patients. In blacks, breast cancer was diagnosed in a relatively more advanced stage than in whites. Survival and cure rates were generally lower for blacks, and such lower rates seem to be associated with the relatively advanced stage of the disease.

Results from the standpoint of survival rates and locoregional failures are compared in three series of patients having had a radical mastectomy for breast cancer: (1) radical mastectomy alone for the patients who had essentially outer quadrant lesions and a negative axilla; (2) postoperative irradiation when the axillary nodes were positive and/or the tumor was centrally located or in the inner quadrants; and (3) preoperative irradiation for patients with an outside biopsy presenting with a very disturbed breast with edema and ecchymosis, and in a small group of patients with a lesion of clinically borderline operability. The ten-year survival rates are identical in the three groups. In the radical mastectomy alone group, 14% of the patients had positive axillary nodes, in the preoperative irradiation group 30% (probably one half of the true incidence without preoperative irradiation), and in the postoperative group, 71%. This data is indicative that irradiation, either pre- or postoperatively, has survival benefits since there is direct relationship between the percentage of patients with positive axillary nodes and the survival rates. However, there is no evidence that preoperative irradiation is superior to postoperative irradiation.

Two long-term survivors with nodular sclerosing Hodgkin's disease were found to have adenocarcinoma of the breast sixteen and twenty years after limited field radiotherapy. Examination of the axillary nodes at radical mastectomy showed both metastatic adenocarcinoma and clinically inapparent Hodgkin's disease. The occurrence of persistent but clinically inactive Hodgkin's disease as well as the development of secondary malignancies in this disease has important clinical ramifications. Skin testing and in vitro lymphocyte transformation studies in these two patients were also done.

Surveys of surgical practice in the United States during the last 2 decades have documented a gradual retreat from the standard radical mastectomy for treatment of early breast cancer. During this time, clinical trials have tested traditional principles of cancer surgery, and permitted conclusions to be made regarding treatment alternatives. Modified mastectomy (total mastectomy plus axillary dissection) has proved equal to radical mastectomy in terms of survival, disease-free survival, and local tumor control in a randomized trial confined to TNM clinical Stage I and II cases. This study showed that routine removal of grossly uninvolved pectoral muscles (and apical axillary nodes) is not necessary in early cases, a result which failed to support the principle of en bloc dissection. Trials addressed to the practice of prophylactic regional node dissections have indicated that node dissections are useful for reducing regional tumor recurrence, for providing prognostic information, and for establishing the need for adjuvant treatment, but they do not improve overall survival. Metastases in lymph nodes appear to be a sign, rather than a source, of tumor dissemination. Furthermore, a recent trial indicates that routine removal of the breast may not be necessary in early cases. High-dose irradiation of the breast (after wide excision of the primary and axillary dissection) in TNM clinical Stage I cases provided local tumor control and survival comparable to that of radical mastectomy. Trials of breast preservation not yet complete address more advanced stages (TNM I and II), and the question of whether irradiation is necessary in all cases. On the basis of completed studies, it appears that TNM clinical State I and II cancers can be appropriately treated with modified mastectomy; Stage I cancers can be treated equally well with irradiation of the breast after quadrantectomy and removal of axillary lymph nodes.

Since 1960 more than 3000 consecutive patients with operable infiltrating breast carcinoma were treated by radiation therapy with or without primary limited surgery, which usually consisted of local excision. For tumors smaller than or equal to 5 cm the ten-year crude survival rate is 77% for patients without palpable axillary nodes (T/sub 1-2/N/sub 0/) and 63% for patients having axillary adenopathy (T/sub 1-2/N/sub 1/). For operable tumors exceeding 5 cm in diameter (T/sub 3/N/sub 0-1/) the ten-year crude survival is 34%. Thirty-five percent of the patients alive free of disease at ten years required a secondary operation for presumed local or regional tumor persistence or recurrence, although no residual disease was found in 24% of the operative specimens. Local-regional recurrence had no adverse effect on ten-year survival. This conservative approach offers most women with operable breast cancer an excellent chance at breast preservation with the same chance for ten-year survival as with radical mastectomy.

The records of 716 consecutive patients with breast cancer randomized from January 1964 to January 1968 between radical and extended radical mastectomy not followed by postoperative radiation therapy were reviewed. Relapse and survival rates were related to different patterns with the intent to define, on clinical basis, the high-risk groups in whom systemic adjuvant treatment can be attempted. The 10-year relapse rate was 52.9% for the whole series. In patients with negative axillary nodes (N-) this finding was 27.9% compared to 75.5% for patients with positive nodes (N+ 1-3: 66.5%, N+ greater than 3: 83.6%). The relapse rate was also affected by concomitant involvement of internal mammary nodes (IMN): N- IMN+: 60%, N+ IMN+: 96.7%. The corresponding 10-year survival rates were as follows: 59.7% (total), 81.9% (N-), 39.6% (N+), 53.7% (1-3), 25.6% (greater than 3), 45.8% (N- IMN+), 20.5% (N+ IMN+). In N+ patients relapse and survival rates were directly proportional to the size of primary tumor, while this trend was not present in N- patients. Location of primary tumor as well as menopausal status showed no direct effect on relapse and survival. In both nodal groups the sites of first relapse were documented to occur preferentially in distant organs and tissues.

In 24 patients undergoing radical mastectomy, the degree of sensitization to breast cancer was compared between lymphocytes obtained from regional lymph nodes and circulating lymphocytes. Using the direct lymphocyte migration inhibition assay a greater immunologic response was observed in regional lymph node lymphocytes as compared to circulating lymphocytes when challenged with breast cancer antigen in vitro. In the breast cancer group, migration inhibition (M.I.) was 21% plus or minus 3% in the regional lymph node (R.L.N.) lymphocytes, as compared to 7% plus or minus 3% in the peripheral blood (P.B.) lymphocytes (p smaller than .01). In the control group M.I. was - 10% plus or minus 2% in the R.L.N. lymphocytes, as compared to - 2% plus or minus 3% in the P.B. lymphocytes (p equal to n.s.) indicating no immunologic response to the breast cancer antigen. A significant delayed hypersensitivity response (M.I.greater 20%) was found in 17/24 regional lymph nodes of the radical mastectomy graoup, as compared to 7/24 in the peripheral blood samples tested in the same group, indicating a superior immune response in the regional lymph node lymphocyte population. These data support the concept that regional lymph nodes in breast cancer patients are immunologically competent, and that the lymphocytes in these nodes are more reactive with a tumor antigen than are the circulating lymphocytes.

In 1963 an electron beam became available, making irradiation of the chest wall technically easy. In addition to peripheral lymphatic irradiation in patients with positive axillary nodes and/or the tumor in the inner quadrants or centrally located, patients with tumor larger than 5 cm or with grave signs and/or a significant incidence of positive axillary nodes received chest wall irradiation. None of the patients has received elective chemotherapy. Disease-free survival rates at ten years are 54% for the overall group, 79% for the patients with negative nodes, 44% for patients with positive nodes, 61% for patients with 1-3 positive nodes, and 33% for patients with four or more positive nodes. The incidence of peripheral lymphatic failures is low as well as the incidence of failures on the chest wall in the patients having had chest wall irradiation. With the availability of electron beam and adjustments in doses, complications are nonexistent. The incidence of treatment failures, local-regional, or distant, that have appeared by ten years are compared with the incidence of failures that were experienced by the placebo patients in the clinical trial of the NSABP of thio-TEPA versus placebo. The clearly lesser incidence of treatment failures in the U.T.M.D. Anderson Hospital patients either suggests that postoperative irradiation may have survival benefits or that the data of the NSABP series are not representative of all series.

The relationship of the levels of selected urinary steroid metabolites to breast cancer recurrence after radical mastectomy was studied. An analysis of variance of the steroid measurements suggested that the measurements standardized to per gram of creatinine were the appropriate measure to use in exploring these relationships. No significant associations were found for premenopausal patients; however, for postmenopausal patients, low levels of total 17-ketosteroids were associated with a reduced two-year recurrence-free rate whereas low and high levels of OHA and high levels of total estrogens were associated a relatively low high two-year recurrence-free rate. Because of the large number of significance tests performed and the lack of consistent patterns, it is questionable whether the observed associations are of any importance. Including these steroid quantities in a multivariate regression model along with previously determined clinical prognostic factors indicated that the steroid determinations were the least important variables and did not make a significant contribution to the fit of the model.

This presumptive study concerns the value of lumpectomy as a curative procedure for minimal breast carcinoma, defined as an operable cancer no larger than 2 cm in diameter, with no palpable axillary lymph nodes, and, in peripherally located lesions, no Paget's disease. From 199 surgically treated mammary cancer patients, 40 cases met the minimal criteria. Thirty-eight of the minimal breast carcinoma patients had a radical mastectomy and two had a supraradical procedure. The pathology findings and survival data were analyzed in these minimal carcinoma cases, and it was calculated that lumpectomy alone would have left cancer cells in 48% of the patients because of regional lymph node involvement by cancer, extension of cells from a peripheral cancer to the nipple ducts, or presence of a second carcinoma in the breast. However, the estimated 30-year cure rate in these radical surgically treated patients was 86%.

Pleomorphic adenoma of the human breast is a rare, benign tumor for which the literature is sparse. A local recurrence has been reported only once before. The diagnostic challenge of this cancer-imitating lesion is emphasized in this report. Although local excision of the tumor is the treatment of choice, almost SOW of the patients reported have undergone fairly extensive surgery, i.e., simple or radical mastectomy. A paraffin section of the excised tumor is mandatory to confirm the benign nature of the lesion to avoid an unnecessary mastectomy for a benign condition. Cancer 61:997-1001,1988. LEOMORPHIC ADENOMA OF THE HUMAN BREAST is P a benign and rare tumor that is histologically identical to similar tumors found in the salivary glands. This "mixed tumor" was not recognized in the English literature until 1969, when Smith and Taylor' reported nine cases encountered during a survey of breast tumors containing bone and cartilage which were on file at the Armed Forces Institute of Pathology, Makek and von Hochstette? added additional cases and reviewed the literature, summarizing relevant findings in the 18 published cases. Since 1980, only two cases of pleomorphic adenoma of the breast have been reported in the English and German literat~re.~.~ The present case is described to emphasize the diagnostic challenge of this benign breast tumor, which is easily mistaken for a malignant tumor clinically, radiologically, and path~logically.~"

The authors report the findings in 107 women who are known to have survived 25 years from among a population of 746 consecutive patients who underwent radical mastectomy for breast carcinoma at the University of Chicago Hospitals and Clinics from 1929 to 1955. Of these patients, 103 had invasive carcinomas, two had intraductal carcinomas, and two had subareolar papillomatosis. Six patients had to be excluded because of inadequate pathologic material. The pathologic findings in 93 cases were compared with those in an equal number of control cases dying within a comparatively short period (median, 3.4 years; range 0.9–9.9 years) after radical mastectomy. These were matched for age, tumor size, and number of positive nodes. Only two of our patients suffered recurrences, and none died of her original tumor; however, 12 developed second primaries in the opposite breast, and four died from them. Compared with all patients who underwent radical mastectomy in this period, the 25-year survivors were younger (69 versus 43% were younger than age 50 years), had smaller tumors (39 versus 26% less than 2 cm in diameter), and a larger number (60 versus 39%) had negative nodes. Nonetheless, 12% of the survivors had tumors larger than 5 cm in diameter and 11% had four or more positive nodes. Histologically, 19% of the 25-year survivors had medullary, mucoid, infiltrating lobular, tubular or lipid rich carcinomas, whereas there was only one lobular and one apocrine carcinoma in the control group. Compared with controls, the survivors had a higher percentage of Grade I tumors and a lower incidence of lymphatic and vascular invasion in the breast. Only one 25-year survivor compared with 16 controls had blood vessel invasion. A surprising 63% of the 25-year survivors had lymphatic or vascular invasion within the tumor, or lymph node metastases compared with 82% of controls. While our studies confirm the importance of these well-known prognostic indicators, it also shows that some patients with pathologically unfavorable lesions, i.e.

The surgical treatment of primary breast cancer must cope with its multicentric origin, its occasional bilaterality, and its primary lymphatic drainage to the axillary and internal mammary nodes. The scope of the surgical procedure should correlate with the extent of disease in the individual patient with the primary aid of removing all disease present in these areas. We have used and continue to use three operative procedures--modified mastectomy (total mastectomy with thorough axillary dissection), radical mastectomy, and extended radical mastectomy. With this selected approach, we have attained a ten-year survival rate of 57% with a 4% local recurrence rate as the first sign of recurrent cancer--8.3% overall local recurrence rate--in a group of 515 patients with infiltrating cancer and 44% proven axillary nodal involvement treated between 1955 and 1964. This includes Stages I, II and III cases. These data are crude and uncorrected for age, intercurrent disease, and lost to follow-up. Forty-three percent of patients received adjuvant x-radiation therapy--4500 rads T.D. to the peripheral nodes. No chemotherapy was given. Similar local control and long term salvage has not been attained by conservative surgery with aggressive x-ray therapy. Long term follow-up--ten years at the minimum--with accurate information regarding extent of disease (nodal status), local recurrence, and survival rate is essential to evaluate the efficacy of a treatment regimen for primary breast cancer.