Roger L. Christian

Preoperative therapy with trastuzumab and paclitaxel followed by sequential adjuvant doxorubicin/cyclophosphamide for HER2 overexpressing stage II or III breast cancer: a pilot study.

PURPOSE Trastuzumab combined with chemotherapy improves outcomes for women with human epidermal growth factor receptor 2 (HER2) overexpressing advanced breast cancer. We conducted a pilot study of preoperative trastuzumab and paclitaxel, followed by surgery and adjuvant doxorubicin and cyclophosphamide chemotherapy in earlier stage breast cancer. PATIENTS AND METHODS Patients with HER2-positive (2+ or 3+ by immunohistochemistry) stage II or III breast cancer received preoperative trastuzumab (4 mg/kg x 1, then 2 mg/kg/wk x 11) in combination with paclitaxel (175 mg/m(2) every 3 weeks x 4). Patients received adjuvant doxorubicin and cyclophosphamide chemotherapy following definitive breast surgery. Clinical and pathologic response rates were determined after preoperative therapy. Left ventricular ejection fraction and circulating levels of HER2 extracellular domain were measured serially. RESULTS Preoperative trastuzumab and paclitaxel achieved clinical response in 75% and complete pathologic response in 18% of the 40 women on study. HER2 3+ tumors were more likely to respond than 2+ tumors (84% v 38%). No unexpected treatment-related noncardiac toxicity was encountered. Four patients developed grade 2 cardiotoxicity (asymptomatic declines in left ventricular ejection fraction). Baseline HER2 extracellular domain was elevated in 24% of patients and declined with preoperative therapy. Immunohistochemical analyses of posttherapy tumor specimens indicated varying patterns of HER2 expression following trastuzumab-based treatment. CONCLUSION Preoperative trastuzumab and paclitaxel is active against HER2 overexpressing early-stage breast cancer and may be feasible as part of a sequential treatment program including anthracyclines. The observed changes in cardiac function merit further investigation. Correlative analyses of HER2 status may facilitate understanding of tumor response and resistance to targeted therapy.

The Utility of Ultrasonographically Guided Large-Core Needle Biopsy Results From 500 Consecutive Breast Biopsies

Five hundred ultrasonographically guided large‐core needle breast biopsies of solid masses were performed in 446 women. Histopathologic results were correlated with imaging findings. Ultrasonographically guided large‐core needle biopsy resulted in diagnosis of malignancy (n = 124) or severe atypical ductal hyperplasia (n = 4) in 128 lesions (26%). In the remaining 372 lesions (74%), ultrasonographically guided large‐core needle biopsy yielded benign pathologic results. Follow‐up of more than 1 year (n = 225), results of surgical excision (n = 50), or both were obtainable in 275 (74%) of the benign lesions. No malignancies were discovered at surgical excision or during follow‐up of this group of benign lesions. There were no complications related to large‐core needle biopsy that required additional treatment. Ultrasonographically guided large‐core needle biopsy is a safe and accurate method for evaluating breast lesions that require tissue sampling.

Sentinel Node Biopsy is Important in Mastectomy for Ductal Carcinoma In Situ

BackgroundThere is uncertainty about the utility of sentinel node biopsy (SNB) for ductal carcinoma in situ (DCIS) and its potential to avoid axillary lymph node dissection (ALND) in patients undergoing mastectomy for DCIS.MethodsA review was conducted of 179 patients who underwent mastectomy with sentinel node biopsy for DCIS without invasion or microinvasion on premastectomy pathology review.ResultsThe sentinel node identification rate was 98.9% (177/179). Twenty (11.3%) of 177 mastectomies for DCIS had a positive SNB: two micrometastasis (pN1mi) and 18 isolated tumor cells [pN0(i+)]. Unsuspected invasive cancer was found in 20 (11.2%) of 179 mastectomies, eight T1mic, five T1a, three T1b, and four T1c tumors. Sentinel nodes were identified in 19 of 20 patients with invasive cancer and four were positive: one pN1mi and three pN0(i+). Eighteen of 19 patients with unsuspected invasive cancer were able to avoid axillary dissection on the basis of SNB results. Of the 159 patients whose final pathology revealed DCIS without invasion, a sentinel node was identified in 158 (99.4%). The SNB was positive in 16 patients (10.1%): one pN1mi and 15 pN0(i+). Three patients underwent ALND on the basis of positive SNBs and in each the SNB was the only positive node.Conclusions11% of patients undergoing mastectomy for DCIS were found to have invasive cancer on final pathology. The use of SNB during mastectomy for DCIS allowed nearly all such patients to avoid axillary dissection. These results support routine use of SNB during mastectomy for DCIS.

Predictive value of sentinel lymph node biopsy prior to neoadjuvant chemotherapy in clinically node negative breast cancer

606 Background: Applicability and optimal timing of sentinel node biopsy (SNB) in breast cancer patients treated with neoadjuvant therapy is not yet known. SNB prior to neoadjuvant therapy is relatively untested, while SNB after neoadjuvant therapy is associated with lower mapping success and higher false negative rates. SNB prior to neoadjuvant therapy may give data useful in guiding systemic, radiation and surgical treatment decisions. METHODS 52 T2-T4, N0 breast cancer patients who had SNB prior to neoadjuvant therapy from 7/2000 to 10/2003 were reviewed. Initial 1° tumor size, SNB pathology, clinical response to therapy and findings at definitive surgery were examined. RESULTS 22 patients (42%) were SNB(-) and 21 had no further axillary treatment. None have recurred locally. 1 SNB(-) patient had tumor progression during chemo and a positive axillary node dissection (ALND). 30 patients (58%) were SNB(+); to date 26 have had ALND after neoadjuvant therapy; 1 with a micromet had no further surgery. At ALND for initially SNB(+), 17 (65%) were node negative, 4(15%) had micromets <0.2cm, and only 5(19%) had residual axillary macromets. Residual tumor sizes ranged from 0-9.0cm (median 2.0cm, 5 tumors >4cm) in 21 SNB(+) with (-) or micromet-only ALNDs. In 5 SNB(+) with macromets on ALND, residual tumor sizes ranged from 0.3- 5.2cm. CONCLUSIONS There were no early axillary relapses in patients with (-)SNBs prior to neoadjuvant therapy. The majority of clinically N0 breast cancer patients with (+) SNBs prior to neoadjuvant therapy will have minimal residual axillary disease at ALND. Among SNB(+)s, residual 1° tumor size did not predict ALND status. These data suggest it may be possible to explore less morbid alternatives to axillary dissection in clinically N0 patients undergoing neoadjuvant therapy. [Figure: see text] No significant financial relationships to disclose.