Breast Surgery Division

Introduction
The number of breast carcinomas is increasing in Japan, and the number of patients in outpatient clinic reflects that increase. We performed 377 operations on breast carcinomas and 12 breast lesions such as phyllodes tumor in 2001.

Routine Activities
This division consists of three full-time surgeons, one chief resident, and two or three surgical residents. Breast conserving treatments (BCT) have gradually increased in number. BCT involves local surgical excision of the tumor and level II axillary dissection followed by postoperative irradiation of the remaining breast.
Indications for BCT are tumors with a diameter of 3 cm or less and the absence of hard lymph nodes on palpation. Patients with multifocal cancer or marked calcifications detected by mammography are not suitable BCT candidates. We are performing neoadjuvant chemotherapy or endocrine therapy to avoid mastectomy for larger tumors. This also functions as an in vivo chemo-sensitivity test and is reflected in the adjuvant therapy. Increasingly we are integrating surgery, radio-therapy, and chemoendocrine therapy. Patients receive adjuvant chemoendocrine therapy according to their prognostic and predictive factors. Significant prognostic factors include the number of lymph nodes involved, followed by the tumor s histological grade, p53, HER2/neu (c-erbB2), and so on. Widely accepted factors which predicts response to a specific therapy are estrogen and progesterone receptors, and HER2/neu.
A weekly conference is held on Wednesday from 16:30 to 17:30 in order for surgeons, medical oncologists, and radiologists to discuss the diagnosis, operative procedures, and adjuvant chemoendocrine therapy of each patient. The diagnostic images are reviewed with the comparison of pathological reports in every postoperative patients.
A monthly breast conference is held on the last Wednesday from 17:30 to 19:00. A monthly theme (e.g., a new protocol study, problems in diagnostic imaging, pathologically interesting cases) is discussed among doctors involved in the breast cancer field, including participants from other hospitals.

Research Activities
These days, the impact of local failure on ultimate outcome in breast cancer treated with BCT is reevaluated and obtaining clear surgical margins is given attention to avoid local failure. The preoperative identification of an extensive intraductal component (EIC) and small invasive foci such as multicentricity and daughter lesions are important factors determining the extent of breast resection required. We have obtained satisfactory results with contrast-enhanced helical computed tomography (CE-CT) to detect them (Akashi- Tanaka et al). We use CE-CT to determine the extent of resection prior to performing breast conserving surgery and to determine the extent of residual disease after neoadjuvant chemotherapy (Akashi-Tanaka et al). The excellent spatial resolution of this procedure allows visualization of small nonpalpable invasive cancers and invasive lobular carcinomas which cannot be demonstrated by other modalities.
Inherited mutant BRCA1 and BRCA2 account for 20-40% of high-risk families in Japan, and therefore at least one more gene (BRCA3?) is required to explain dominantly inherited susceptibility to breast cancer. Ductal hyperplasia and adenosis were typical pathological background features of BRCA1/2-associated breast cancers (Fukutomi et al). This pathological character is also observed in premenopausal patients of familial breast cancer (Fukutomi et al).
With the recent improvements in diagnostic imaging, we have encountered numerous noninvasive cancers. The biological character and the invasive steps in breast cancer progression are of particular interest.We are planning to characterize genetic alterations to make a comparison of invasive ductal carcinoma with in situ components of invasive ductal carcinoma by molecular analysis.

Clinical Trials
1) Adjuvant therapy
After surgery every patient at high risk for re-currence receives adjuvant chemoendocrine therapy according to the international consensus meetings. Treatment strategy is stratified by hormone receptor status, axillary lymph node status, histological grade and menopausal status. Only patients with negative axillary lymph nodes with low nuclear grade cancers receive no adjuvant therapy. For premenopausal patients with receptor positive cancer, LH-RH agonists plus tamoxifen have become a treatment option as adjuvant setting. A randomized phase II study of LH-RH agonist TAP-144-SR (3 months vs 1 month) is underway. For the patients with node positive and receptor negative breast cancer, new multiinstitutional randomizsed clinical trial comparing Taxans and doxorubicin (ADM) will soon start (NSAS BC-02). The results of the N-SAS-BC01 protocol are awaited in which oral UFT and standard CMF were compared in patients with high histological grade cancers without nodal involvement.
2) Neoadjuvant therapy
A randomised, double-blinded, international multi-center study comparing new aromatase inhibitor (Anastrozol) with Tamoxifen as neo-adjuvant treatment (PROACT) is ongoing. Eligible criteria is postmenopausal women with large operable (T2 (>3cm), T3, N0-2, M0) or potentially-operable, locally advanced (T4b, N0-2, M0), ER+ and/or PR+ breast cancer. The primary endpoint is the objective tumor response at 3 months.
For pre-menopausal women with any hormone receptor status and post-menopausal women with negative hormone receptor status, with locally advanced breast carcinoma (T>3cm) a neoadjuvant chemotherapy study (phase II) is ongoing. One hundred and sitxy-five patients have been given the trial regimen of neoadjuvant chemotherapy using docetaxel and doxorubicin, and they have shown a remarkably good clinical response (CR+PR=86%).

S. AKASHI-TANAKA

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