Prospective Feasibility Trial of Sentinel Lymph Node Biopsy in the Setting of Inflammatory Breast Cancer

Background

Most inflammatory breast cancer (IBC) patients have axillary disease at presentation. Current standard is axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NACT). Advances in NACT have improved pathologic complete response (pCR) rates increasing interest in performing sentinel lymph node (SLN) biopsy (SLNB). Previous studies on SLNB for IBC patients did not assess nodal response with imaging or use dual tracer mapping. We sought to prospectively determine false negative rates of SLNB in IBC patients using dual tracer mapping, and to correlate pathology with preoperative axillary imaging.

How many sentinel lymph nodes are enough during sentinel lymph node dissection for breast cancer?

BACKGROUND.: It remains unclear how many sentinel lymph nodes (SLNs) must be removed to accurately predict lymph node status during SLN dissection in breast cancer. The objective of this study was to determine how many SLNs need to be removed for accurate lymph node staging and which patient and tumor characteristics influence this number. METHODS.: The authors reviewed data for all patients in their prospective database with clinical tumor, lymph node, metastasis (TNM) T1 through T3, N0, M0 breast cancer who underwent lymphatic mapping at their institution during the years 1994 through 2006. There were 777 patients who had at least 1 SLN that was positive for cancer. Simple and multiple quantile regression analyses were used to determine which patient and tumor characteristics were associated with the number of positive SLNs. The baseline number of SLNs that needed to be dissected for detection of 99% of positive SLNs in the total group of patients also was determined. RESULTS.: The mean number of SLNs removed in the 777 lymph node-positive patients was 2.9 (range, 1-13 SLNs). Greater than 99% of positive SLNs were identified in the first 5 lymph nodes removed. On univariate analysis, tumor histology, patient race, tumor location, and tumor size significantly affected the number of SLNs that needed to be removed to identify 99% of all positive SLNs. On multivariate analysis, mixed ductal and lobular histology, Caucasian race, inner quadrant tumor location, and T1 tumor classification significantly increased the number of SLNs that needed to be removed to achieve 99% recovery of all positive SLNs. CONCLUSIONS.: In general, the removal of a maximum of 5 SLNs at surgery allowed for the recovery of >99% of positive SLNs in patients with breast cancer. The current findings indicated that tumor histology, patient race, and tumor size and location may influence this number.     

Use of lymphoscintigraphy defines lymphatic drainage patterns before sentinel lymph node biopsy for breast cancer

BACKGROUND: Lymphoscintigraphy (LSG) can identify lymphatic drainage patterns before sentinel lymph node (SLN) biopsy is performed in patients with early-stage breast cancer, but the importance of extraaxillary SLNs seen on LSG is unknown. We assessed whether drainage patterns seen on LSG were associated with histologic findings in axillary SLNs recovered at SLN biopsy. STUDY DESIGN: From a prospectively maintained database, we identified 1,201 clinically node-negative patients with invasive breast cancer who underwent preoperative LSG and axillary SLN biopsy. Patient and tumor characteristics, LSG results, and final SLN pathology results were examined. RESULTS: LSG showed drainage to internal mammary (IM) nodes in 1.6% of patients, axillary nodes in 68.1%, both IM and axillary nodes in 19.8%, and no drainage in 10.3%. Drainage to IM nodes was observed for tumors in all quadrants of the breast. Patients with IM drainage had a younger median age than patients without IM drainage (51.8 versus 58.3 years, respectively; p < 0.001). The intraoperative axillary SLN identification rate was higher when axillary drainage was observed on LSG than when it was not observed (98.7% versus 93.0%, respectively; p < 0.001), but the LSG drainage pattern was not associated with pathologic status of the SLN or number of metastatic SLNs. At a median followup of 32 months, 4 patients had regional nodal recurrence. CONCLUSIONS: Almost one-fourth of patients had lymphatic drainage to the extraaxillary lymph nodes, particularly the IM nodes, seen on LSG. Extraaxillary drainage seen on LSG did not preclude identification of axillary SLNs at operation. Longterm followup of patients with lymphoscintigraphic evidence of extraaxillary drainage is needed to determine whether regional and systemic recurrence patterns differ in these patients.     

Neoadjuvant Chemotherapy in Invasive Lobular Carcinoma May Not Improve Rates of Breast Conservation

Background  Patients with invasive lobular carcinoma (ILC) experience a lower pathological complete response rate to neoadjuvant chemotherapy than patients with invasive ductal carcinoma. This study was intended to evaluate the impact of neoadjuvant chemotherapy in ILC on breast-conserving surgery (BCS) rates. Methods  Two-hundred eighty-four consecutive patients with pure ILC treated between May 1998 and September 2006 were reviewed. Surgical procedures and long-term outcomes were compared between patients receiving neoadjuvant chemotherapy and those receiving surgery first. Results  Neoadjuvant chemotherapy was administered to 84 patients; 200 patients underwent surgery first. The mean tumor size in the neoadjuvant group (4.9 cm) was significantly larger than in patients who underwent surgery first (2.5 cm, p < 0.0001). In the neoadjuvant group, clinical complete response was seen in 10% and partial response in 59%. Overall BCS rates were 17% in the neoadjuvant group compared with 43% in the surgery-first group (p < 0.0001). When controlled for initial tumor size, there was no difference (all p > 0.05) between the groups in terms of (1) the proportion of patients who underwent an initial attempt at BCS, (2) rate of failure of BCS or (3) the proportion of patients undergoing BCS as their final procedure. With a mean follow-up of 47 months, local recurrence (LR) rates were similar between the two groups (1.2% versus 0.5%, p = 0.5). Conclusion  The use of neoadjuvant chemotherapy does not increase the rates of breast conservation in patients with pure ILC.     

The Role of Contralateral Prophylactic Mastectomy in Invasive Lobular Carcinoma

Abstract: Invasive lobular carcinoma has been associated with an increased risk of contralateral breast disease. Controversy exists regarding the use of contralateral prophylactic mastectomy versus careful observation of the contralateral breast. Our objective was to determine the incidence of occult cancer in the contralateral breast and to assess whether contralateral prophylactic mastectomy improves patient survival. We retrospectively reviewed the charts of 133 patients treated surgically for invasive lobular carcinoma between January 1, 1978, and December 31, 1993. The median age was 54 years (range, 24–82 years). The distribution of patients by stage was as follows: stage 1, 29%; stage IIa, 36%; stage IIb, 20%; stage IIIa, 11%; stage IIIb, 3%; and unknown, 1%. The median follow-up was 68 months (range, 13–178 months). Group comparisons were performed using log-rank analysis and survival curves were constructed by the method of Kaplan and Meier. Eighteen patients underwent contralateral prophylactic mastectomy. Among these patients there were no cases of invasive cancer and only 3 (17%) cases of lobular carcinoma in situ in the contralateral breast. Three patients who underwent contralateral prophylactic mastectomy later developed distant metastases from the original ipsilateral breast cancer. Of the 115 patients managed conservatively, 3 (3%) developed contralateral disease at 11, 34, and 101 months. Twenty-five patients developed distant disease. Overall survival in the contralateral prophylactic mastectomy group did not differ significantly from the group treated conservatively (p = 0.90). We conclude that careful observation with a yearly mammogram and physical examination of the contralateral breast is appropriate management for patients with invasive lobular carcinoma.     

Validation of a Breast Cancer Nomogram for Predicting Nonsentinel Lymph Node Metastases After a Positive Sentinel Node Biopsy

Background Although completion lymph node dissection (CLND) is the standard of care for breast cancer patients with sentinel lymph node (SLN) metastases, the SLN is the only node with tumor in 40% to 60% of cases. To assist with decision-making regarding CLND, investigators at Memorial Sloan-Kettering Cancer Center devised and validated a nomogram for predicting the likelihood of non-SLN metastases. To assess the generalizable use of this nomogram, validation analysis was performed by using an external database. Methods Eight clinicopathologic variables for 200 consecutive breast cancer patients at the University of Texas M. D. Anderson Cancer Center with SLN metastases and CLND were entered into the nomogram. The accuracy of the nomogram to predict non-SLN metastases was assessed by the receiver operating characteristic (ROC) curve and linear regression analysis. The accuracy of the nomogram with touch-imprint cytology (TIC) as a substitute variable for frozen section was also evaluated. Results The linear correlation coefficient of the nomogram-predicted probabilities correlated with the observed incidence of non-SLN metastases for all patients (.97). The accuracy of the nomogram as measured by the area under the ROC curve was .71. When applied solely to patients who had TIC assessment of the SLN, the area under the ROC curve was .74. Conclusions This study validated the Memorial Sloan-Kettering Cancer Center breast cancer nomogram by using an external database. TIC seems to be an acceptable substitute for frozen section as a nomogram variable. The nomogram may help predict an individual’s risk of non-SLN metastases and assist in patient decision making regarding the benefit of CLND. Presented at the Annual Meeting of the Society of Surgical Oncology, Atlanta, Georgia, March 3–6, 2005.     

Cytologically proven axillary lymph node metastases are eradicated in patients receiving preoperative chemotherapy with concurrent trastuzumab for HER2‐positive breast cancer

BACKGROUND:

The axillary pathologic complete response rate (pCR) and the effect of axillary pCR on disease‐free survival (DFS) was determined in patients with HER2‐positive breast cancer and biopsy‐proven axillary lymph node metastases who were receiving concurrent trastuzumab and neoadjuvant chemotherapy. The use of neoadjuvant chemotherapy is reported to result in pCR in the breast and axilla in up to 25% of patients. Patients achieving a pCR have improved DFS and overall survival. To the authors' knowledge, the rate of eradication of biopsy‐proven axillary lymph node metastases with trastuzumab‐containing neoadjuvant chemotherapy regimens has not been previously reported.

METHODS:

Records were reviewed of 109 consecutive patients with HER2‐positive breast cancer and axillary metastases confirmed by ultrasound‐guided fine‐needle aspiration biopsy who received trastuzumab‐containing neoadjuvant chemotherapy followed by breast surgery with complete axillary lymph node dissection. Survival was evaluated by the Kaplan‐Meier method. Clinicopathologic factors and DFS were compared between patients with and without axillary pCR.

RESULTS:

Eighty‐one patients (74%) achieved a pCR in the axilla. Axillary pCR was not associated with age, estrogen receptor status, grade, tumor size, initial N classification, or median number of lymph nodes removed. More patients with an axillary pCR also achieved a pCR in the breast (78% vs 25%; P < .001). At a median follow‐up of 29.1 months, DFS was significantly greater in the axillary pCR group (P = .02).

CONCLUSIONS:

Trastuzumab‐containing neoadjuvant chemotherapy appears to be effective in eradicating axillary lymph node metastases in the majority of patients treated. Patients who achieve an axillary pCR are reported to have improved DFS. The success of pCR with concurrent trastuzumab and chemotherapy in eradicating lymph node metastases has implications for surgical management of the axilla in these patients. Cancer 2010. © 2010 American Cancer Society.     

Prospective Evaluation of the Nipple–Areola Complex Sparing Mastectomy for Risk Reduction and for Early-Stage Breast Cancer

Background

Psychological effects of mastectomy for women with breast cancer have driven treatments that optimize cosmesis while strictly adhering to oncologic principles. Although skin-sparing mastectomy is oncologically safe, questions remain regarding the use of nipple–areola complex (NAC)-sparing mastectomy (NSM). We prospectively evaluated NSM for patients undergoing mastectomy for early-stage breast cancer or risk reduction.

Methods

We enrolled 33 early-stage breast cancer and high-risk patient; 54 NSMs were performed. NAC viability and surgical complications were evaluated. Intraoperative and postoperative pathologic assessments of the NAC base tissue were performed. NAC sensory, cosmetic and quality of life (QOL) outcomes were also assessed.

Results

Twenty-one bilateral and 12 unilateral NSMs were performed in 33 patients, 37 (68.5%) for prophylaxis and 17 (31.5%) for malignancy. Mean age was 45.4 years. Complications occurred in 16 NACs (29.6%) and 6 skin flaps (11.1%). Operative intervention for necrosis resulted in 4 NAC removals (7.4%). Two (11.8%) of the 17 breasts with cancer had ductal carcinoma-in-situ at the NAC margin, necessitating removal at mastectomy. All evaluable patients had nipple erection at 6 and 12 months postoperatively. Cosmetic outcome, evaluated by two plastic surgeons, was acceptable in 73.0% of breasts and 55.8% of NACs, but lateral displacement occurred in most cases. QOL assessment indicated patient satisfaction.

Conclusions

NSM is technically feasible in select patients, with a low risk for NAC removal resulting from necrosis or intraoperative detection of cancer, and preserves sensation and QOL. Thorough pathologic assessment of the NAC base is critical to ensure disease eradication.     

Effective Local Control and Long-Term Survival in Patients with T4 Locally Advanced Breast Cancer Treated with Breast Conservation Therapy

Background: The presence of skin involvement has been accepted as a relative contraindication to breast preservation because it is believed to be associated with an increased local failure rate. This study was conducted to assess the outcome of a carefully selected group of patients who presented with breast cancer involving the skin and who had breast conservation therapy (BCT) following neoadjuvant chemotherapy.Methods: Between 1987 and 1999, 33 patients with stage IIIB or IIIC breast cancer completed treatment consisting of four cycles of neoadjuvant chemotherapy, lumpectomy, radiation therapy, and consolidative chemotherapy. Clinicopathologic factors were analyzed and patients were followed for locoregional and distant recurrence.Results: Initial median tumor size was 7 cm. All patients had skin involvement, defined as erythema, skin edema, direct skin invasion, ulceration, or peau dorange. Following chemotherapy, median pathologic tumor size was 2 cm. Complete resolution of skin changes occurred in 29 patients (88%). At median follow-up time of 91 months in surviving patients, 26 patients (79%) were alive without evidence of disease. The 5-year, disease-free survival rate was 70%, and the 5-year overall survival rate was 78%. The actuarial ipsilateral breast cancer recurrence rate was 6% at 5 years.Conclusions: Patients who present with T4 breast cancer who experience tumor shrinkage and resolution of skin changes with neoadjuvant chemotherapy represent a select group of patients who can have BCT. These patients have favorable rates of long-term local control and survival. Mastectomy is not mandatory for all patients with breast cancer who present with skin involvement.Presented at the 57^th Annual Society for Surgical Oncology Cancer Symposium in New York City, New York, March 18–21, 2004