Shuster TD - Surg Clin North Am - 01-Apr-2000; 80(2): 505-33
From NIH/NLM MEDLINE, HealthSTAR

Full Source Title:
Surgical Clinics of North America

Author Affiliation:
Harvard Medical School, Boston, USA.

Authors:
Shuster TD; Girshovich L; Whitney TM; Hughes KS

Abstract:
Breast cancer management requires a multidisciplinary approach that is tailored to the patient's stage at presentation, desire for breast conservation or reconstruction, estimation of risk of recurrence, and assessment of the benefits and toxicities of potential adjuvant therapies. At the Lahey Clinic Medical Center, breast surgeons, plastic surgeons, radiation oncologists, and medical oncologists staff the Breast Cancer Treatment Clinic, and work closely together to formulate treatment plans that will optimize the likelihood for cure with an acceptable cosmetic result. This involves careful preoperative work-up, surgical axillary staging, breast irradiation in the setting of breast conservation, and selection of chemotherapy or hormonal therapy if appropriate. Newer aspects of breast cancer care, including sentinal lymph node biopsy, postmastectomy radiation therapy, expanded use of hormonal therapy in younger women, new agents and chemotherapy combinations, and autogenous reconstruction techniques, have become an essential part of the multidisciplinary clinic approach.

2) Conservative surgery without radiotherapy in the treatment of patients with early-stage invasive breast cancer. A review.

Recht A - Ann Surg - 01-Jul-1995; 222(1): 9-18
From NIH/NLM MEDLINE

Full Source Title:
Annals of Surgery

Author Affiliation:
Joint Center for Radiation Therapy, Harvard Medical School, Boston, Massachusetts, USA.

Authors:
Recht A; Houlihan MJ

Abstract:
OBJECTIVE: The authors determined whether some patients with clinical stage I or II invasive breast cancer can be adequately treated by conservative surgery without radiotherapy.

SUMMARY BACKGROUND DATA: Currently, there are many patients who are being treated in this manner in both academic and community hospitals. This approach is not as effective as either mastectomy or conservative surgery followed by radiotherapy in preventing local recurrence. However, there may be subsets of patients who might be adequately treated by surgery alone with acceptably low recurrence rates.

METHODS: The authors reviewed retrospective studies of conservative surgery alone and of randomized trials comparing the results of treatment with and without postoperative radiotherapy.

RESULTS: The local recurrence rate is unacceptably high when random patients are treated with conservative surgery without radiotherapy. More favorable results may be possible when relatively wide excisions are performed on selected postmenopausal patients with small lesions without an extensive intraductal component, lymphatic or blood-vessel invasion, and histologically negative axillary nodes. The role of tamoxifen in reducing the risk of breast recurrence is uncertain. Despite salvage therapy, some individuals may develop disseminated disease as a result of local recurrence.

CONCLUSIONS: The authors believe that conducting carefully designed prospective studies of conservative surgery alone is reasonable for patients who are adequately informed of the potential risks of omitting radiation therapy. However, currently, patients should not be treated with conservative surgery alone (without radiotherapy) without such stringent guidelines.

3) Long-term results of breast conservation therapy for breast cancer.

Neff PT - Ann Surg - 01-Jun-1996; 223(6): 709-16; discussion 716-7
From NIH/NLM MEDLINE

Full Source Title:
Annals of Surgery

Author Affiliation:
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA.

Authors:
Neff PT; Bear HD; Pierce CV; Grimes MM; Fleming MD; Neifeld JP; Arthur D; Horsley JS 3rd; Lawrence W Jr; Kornstein MJ

Abstract:
OBJECTIVE: This study was done to determine the long-term outcome of breast conservation therapy (BCT) for patients with early-stage breast cancer during a period of treatment evolution at a single institution.

SUMMARY BACKGROUND DATA: Breast cancer treatment has evolved from extensive surgical extirpation of the breast to treatment options that conserve the breast. Prospective and retrospective studies have confirmed the efficacy of BCT and justify its use for many patients with early breast cancer, but there is no universally accepted consensus as to who benefits from more aggressive application of surgery or radiotherapy in BCT. Prognostic variables for breast cancer and information on factors that contribute to local recurrence help predict BCT results. Continued analysis of BCT still is necessary to improve patient outcome.

METHODS: Eighty-five patients treated with BCT (lumpectomy with adjuvant radiation therapy) at the Medical College of Virginia from 1980 to 1990 were identified. Clinicopathologic parameters and treatment details were analyzed for relationship to development of local recurrence, distant metastasis, and survival. Fisher's exact test was used for comparisons. Actuarial survival curves were plotted. The earlier treatment period (1980-1985) was compared with the later treatment period (1985-1990).

RESULTS: Median follow-up was 5 years. Actuarial overall survival was 83% at 5 years (69% at 10 years), and 5-year distant metastasis-free survival was 79%. The 5-year actuarial local recurrence rate was 6.6% (crude rate 10.6%, 9/85). Young patients (age < 40 years) were found to be at increased risk for local recurrence (24% < 40 years vs. 6% > or = 40 years, p < 0.05). Tumor margins < or = 3 mm were more frequently found, and lumpectomy site radiation boost was used increasingly from 1986 to 1990. Almost half of all local recurrences occurred after 5 years.

CONCLUSIONS: Survival and local recurrence rates were comparable to other series. Young patients were found to be at increased risk for local recurrence. Negative microscopic margins, even when close, can provide low local recurrence rates when adjuvant radiation therapy is administered.

4) MANAGEMENT OF EARLY INVASIVE DISEASE (STAGES I, II)

Source: Abeloff: Clinical Oncology, 2nd ed

The management of early invasive breast cancer today is truly multidisciplinary. Patients should be evaluated by a team of breast cancer specialists representing the subspecialties of surgical oncology, radiation oncology, and medial oncology. It has been estimated that 75 percent of patients with a newly diagnosed breast cancer will have tumors less than 5 cm in diameter with the vast majority being 2 cm or less; of the latter group of patients, 75 percent will be node-negative. For stage I and II disease, patients usually have two options breast conservation or mastectomy with or without reconstruction. A careful histologic assessment of the resected tumor, with particular attention to size, histologic margins, and histology, is important for the decision. Other factors to include are the extent of the intraductal component, the histology of the intraductal component if present, and prognostic information obtained from a study of specific tumor markers. It is most important to determine carefully the patient's needs, expectations, and understanding of available therapeutic options.

The goal of breast conservation is an acceptable cosmetic outcome without sacrificing disease-free survival and overall survival. For some patients, because of tumor size, location, or smaller breast size, the cosmetic result may be better with mastectomy and reconstruction, although this is less of a problem today with the availability of neoadjuvant chemotherapy. However, the loss of a breast can be devastating for some women. The breast is a sign of attractiveness, motherhood, and femininity, and breast removal can cause severe postoperative depression. While these are important factors, studies comparing mastectomy and breast conservation show that the latter does not eliminate the emotional upset formerly attributed to mastectomy. Even patients undergoing breast-preserving therapy suffer from persistent fear regarding the risk of developing recurrence and the possibility of loss of life. These fears impact on the patient and the family much more than the loss of the breast.

One of the major changes in cancer care during the past decade is the increasing use of adjuvant chemotherapy or hormone therapy, or both, in the management of primary breast cancer. It is estimated that in the United States approximately 50 percent of node-negative and 80 percent of node-positive patients receive systemic adjuvant therapy. ^[496]

Increased understanding of the biologic behavior and patterns of spread of breast cancer, advances in cytotoxic chemotherapy and endocrine therapy, and study of these principles in animal tumor models have provided an excellent scientific basis for investigation of adjuvant therapy in humans. These clinical trials have been carried out under the rationale that breast cancer is no longer curable once clinically detectable distant metastases have occurred.

Assessment of the indication for adjuvant therapy in an individual patient should be based on the risk of recurrence and death from breast cancer in the specific patient, the anticipated net benefits of therapy, and other relevant medical and psychosocial factors. Many decisions regarding adjuvant therapy must be based on data that are subject to a wide range of interpretation. That patients be well informed and educated on the pros and cons of such therapy and that they play an active role in the decision-making process cannot be overemphasized. ^[497]

Breast Conservation Therapy Utilizing Surgery and Radiation

Fortunately, for most stage I and II patients breast conservation is an acceptable therapy. The appropriateness of breast conservation has been one of the most studied treatment decisions in modern medicine. In the 1920s and 1930s pioneering investigators, such as Keynes ^[498] in England, Peters ^[499] in Canada, Baclesse ^[500] in France, and Mustakallio ^[501] in Finland, began to treat groups of women with breast-conserving partial mastectomies followed by irradiation to the intact breast, challenging the need for total mastectomy. Results from these early studies were quite promising. Keynes ^[498] and Peters ^[499] compared their breast-conserving results with those of similar staged patients treated contemporaneously with radical surgery. The results showed no differences in survival for patients who elected a breast-sparing approach. Baclesse ^[500] showed that local control could be obtained in a substantial majority of patients treated with radiation as a sole therapy, even in the setting of locally advanced tumors.

A number of single institutions began to embark on nonmastectomy therapy using excision plus radiation for many of their breast cancer patients, at first in European and Canadian centers and later in the United States. In the early 1970s, several European reports created a great deal of interest worldwide in nonmastectomy treatment, since excellent results were being seen in series of several hundred patients. ^{[502] [503]} The first small series in the United States was published in 1975 by Prosnitz and Goldenberg ^[504] from Yale University; soon thereafter the Joint Center for Radiation Therapy in Boston, led by Hellman and colleagues, ^[505] began to publish their results, which were also quite encouraging. To date, dozens of single institution experiences have been reported in the literature. Selected series are presented in Table 75-19 . They have consistently demonstrated

TABLE 75-19 -- SINGLE-INSTITUTION EXPERIENCE WITH EXCISION PLUS RADIATION IN THE TREATMENT OF PRIMARY BREAST CANCER

AUTHOR	NO. OF PATIENTS	DATES	10-YEAR BREASTRECURRENCE RATE (% )
Ayme et al [506]	1,775	1960-1982	13
Heimann et al. [507]	869	1984-1994	3% *
Kini et al [508]	400	1980-1987	10%
Grosse et al. [509]	3,072	1972-1995	10%
Mansfield et al. [510]	1,070	1982-1994	14%
Gage et al. [511]	1,628	1968-1986	13%
Pierce et al. [512]	429	1984-1995	11%
Haffty et al. [513]	973	1970-1989	16%

*5-year rate.

that crude local recurrence rates range from 5 to 10 percent and that survival is equivalent to the expected survival of a group of similar patients treated with mastectomy.

If only single-institution studies made up the mainstay of evidence for the efficacy of breast-sparing therapy, some doubt might remain as to the equivalence of this technique compared with mastectomy. Selection bias in single-institution studies could place more favorable patients into the lumpectomy group, thus creating a false impression of the success of this treatment. The only scientifically valid test of a new treatment is a randomized comparison against standard therapy. To date, six randomized prospective trials comparing lumpectomy plus radiation with mastectomy have been performed and published in the literature. ^{[514] [515] [515A] [516] [517] [518]}

Details of these trials are presented in Table 75-20 . Close to 4,000 women have been randomized between the two therapies; the outcome at 5, 10, and 15 years shows that survival in the two treatment groups is identical. It is inconceivable that these survival curves will ever separate, and thus it can be stated with great certainty that women who choose breast-sparing therapy do not pay a survival price compared with those having a mastectomy. In fact, the data are so convincing that in 1990, the National Center Institute held a Consensus Development Conference on the Treatment of early breast cancer and declared that breast-sparing therapy was not only equivalent to mastectomy but was actually the "preferable" treatment, since it preserved the breast with all the attendant psychological and body image advantages associated with such a lesser surgical procedure. ^[522]