Eleftherios P. Mamounas

Sentinel lymph node biopsy after neoadjuvant systemic therapy

As sentinel node biopsy has emerged as a possible alternative to axillary node dissection in patients with operable breast cancer, this procedure is also emerging as a possible alternative in patients who have received prior neoadjuvant chemotherapy. Initial smaller, single-institution series with the latter approach have shown significant variability in the identification rates and false negative rates resulting in inconsistent--and at times disparate--conclusions regarding the appropriateness of this technique in this group of patients. Subsequent larger, multicenter series have shown, that the identification rates and false negative rates with sentinel node biopsy after neoadjuvant chemotherapy are similar to those when sentinel node biopsy is performed after breast cancer diagnosis. Thus, it appears that the sentinel node concept is also applicable in patients who have undergone neoadjuvant chemotherapy. This observation has the potential to expand the utility of neoadjuvant chemotherapy in patients with operable breast cancer.

Pathologic Complete Response of HER-2 Neu-Positive Invasive Ductal Carcinoma and Ductal Carcinoma In Situ following Neoadjuvant Chemotherapy plus Trastuzumab: A Case Report and Review of Literature

Pathologic complete response (pCR) after NC has been consistently associated with improved outcomes. Residual DCIS after NC does not portray worse prognosis compared to complete eradication of all disease but has clinical implications regarding surgical management. We report a case of pCR of DCIS associated with invasive carcinoma in an HER-2 + tumor after NC plus trastuzumab despite persistence of malignant-appearing microcalcifications mammographically. A 41-year-old Caucasian female presented with a 4 × 4 cm mass in the right breast and a 2.5 cm right axillary node. Mammogram showed a 2.5 cm mass and a 12 cm area of linear pleomorphic, suspicious calcifications in the upper part of the breast. Core biopsy revealed invasive ductal carcinoma and DCIS associated with calcifications (ER 85%, PR 6%, Her2neu 3+ by IHC). Axillary node FNA was positive for malignancy. The patient received doxorubicin/cyclophosphamide (AC) → paclitaxel plus T with complete clinical and radiologic response but no significant change in the microcalcifications. Final pathology showed no residual invasive carcinoma or DCIS despite the presence of numerous ducts with microcalcifications. Documented eradication of DCIS has not been reported following NC when malignant-appearing calcifications persist and this observation may have important clinical implications regarding surgical management.

Tailoring loco-regional therapy with neoadjuvant chemotherapy: another step in the right direction.

The initial goal of neoadjuvant chemotherapy in breast cancer was to convert patients with inoperable disease to operable candidates. The rationale expanded to include patients with large, operable breast cancer in an effort to increase rates of breast-conserving surgery. Several randomized1–3 and nonrandomized trials4–7 have demonstrated that neoadjuvant chemotherapy significantly reduces mastectomy rates in this group of patients. Encouraged by these results, several investigators subsequently demonstrated that neoadjuvant chemotherapy can also reduce mastectomy rates in patients with locally advanced disease without significantly increasing local recurrence rates.8–11 These studies, however, included only a small number of patients with skin involvement, which makes this situation a relative contraindication to breast conservation, even after a good clinical response to neoadjuvant chemotherapy. The study by Shen et al.12 from M. D. Anderson Cancer Center in this issue of the Annals of Surgical Oncology suggests that, even in this group of patients with aggressive locally advanced disease, breast conservation is feasible with reasonably low local recurrence rates. Despite the small numbers included in this study, this report is useful in expanding the potential pool of patients with locally advanced breast cancer in whom a mastectomy can be avoided. Several factors have contributed to the success of breast-conserving surgery following neoadjuvant chemotherapy in patients with locally advanced breast cancer. More active chemotherapy regimens (with the introduction of anthracycline and taxane) have significantly increased clinical and pathologic complete response rates and, thus, have made wide excisions with good cosmetic results possible in a substantial proportion of patients. Newer imaging modalities (e.g., breast magnetic resonance imaging [MRI]) can delineate more accurately than mammography the extent and growth patterns of primary breast tumors and the amount of residual disease following neoadjuvant chemotherapy.13–16 Perhaps, more importantly, MRI can identify several distinct patterns of tumor growth that have been associated with varying response rates17,18 and are predictive of the ability to perform breast-conserving surgery after neoadjuvant chemotherapy.19 The ability to insert radiopaque markers under mammographic or sonographic guidance at the site of the primary tumor has enhanced our ability to identify the exact tumor location in cases of complete clinical or radiologic response or the area of the previous tumor location in cases of pathologic complete response.20–22 Although the original clinical impetus for the use of neoadjuvant chemotherapy in operable and locally advanced breast cancer was to reduce the extent of surgery in the breast and avoid mastectomy, the advent of sentinel node biopsy has introduced another potential benefit with the use of neoadjuvant chemotherapy. Because neoadjuvant chemotherapy downstages axillary lymph nodes in a considerable proportion of patients (up to 40% with anthracycline and taxane-containing regimens),2,3,23,24 it was hypothesized that patients with involved nodes at diagnosis could be spared from an axillary dissection if, after neoadjuvant chemotherapy, sentinel node biopsy revealed negative sentinel node(s). Several single-institution and multicenter studies have examined the question of feasibility and accuracy of sentinel node biopsy following neoadjuvant chemotherapy.25 Although the evidence is much less definitive in this setting compared with performing the procedure before systemic therapy, data viewed collectively indicate that the performance characteristics of sentinel node Received August 2, 2004; accepted August 23, 2004. From the Department of Surgery, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio; and Cancer Center, Aultman Health Foundation, Canton, Ohio. Address correspondence to: Eleftherios P. Mamounas, MD, MPH, FACS, Cancer Center, Aultman Health Foundation, 2600 6th Street, Canton, OH 44710; Fax: 330-363-7367; E-mail: tmamounas@ aultman.com.