Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer.

The purpose of this study is to determine the biologic impact of short-term lipophilic statin exposure on in situ and invasive breast cancer through paired tissue, blood and imaging-based biomarkers. A perioperative window trial of fluvastatin was conducted in women with a diagnosis of DCIS or stage 1 breast cancer. Patients were randomized to high dose (80 mg/day) or low dose (20 mg/day) fluvastatin for 3-6 weeks before surgery. Tissue (diagnostic core biopsy/final surgical specimen), blood, and magnetic resonance images were obtained before/after treatment. The primary endpoint was Ki-67 (proliferation) reduction. Secondary endpoints were change in cleaved caspase-3 (CC3, apoptosis), MRI tumor volume, and serum C-reactive protein (CRP, inflammation). Planned subgroup analyses compared disease grade, statin dose, and estrogen receptor status. Forty of 45 patients who enrolled completed the protocol; 29 had paired Ki-67 primary endpoint data. Proliferation of high grade tumors decreased by a median of 7.2% (P = 0.008), which was statistically greater than the 0.3% decrease for low grade tumors. Paired data for CC3 showed tumor apoptosis increased in 38%, remained stable in 41%, and decreased in 21% of subjects. More high grade tumors had an increase in apoptosis (60 vs. 13%; P = 0.015). Serum CRP did not change, but cholesterol levels were significantly lower post statin exposure (P < 0.001). Fluvastatin showed measurable biologic changes by reducing tumor proliferation and increasing apoptotic activity in high-grade, stage 0/1 breast cancer. Effects were only evident in high grade tumors. These results support further evaluation of statins as chemoprevention for ER-negative high grade breast cancers.

Reoperative sentinel lymph node biopsy: a new option for patients with primary or locally recurrent breast carcinoma.

BACKGROUND: Sentinel lymph node (SLN) biopsy is a new standard of care for axillary node staging in patients with primary operable breast cancer. An increasing proportion of these patients undergo breast-conserving surgery, and 10% to 15% will develop local relapse requiring reoperation. Although previous breast or axillary surgery is often considered a contraindication to SLN biopsy, few data support this position. We report our experience with SLN biopsy in the reoperative setting. STUDY DESIGN: We examined the 3,490 consecutive SLN biopsy procedures for breast cancer performed at our institution between September 1996 and July 2001; 32 (1%) of these followed previous axillary surgery: 22 (69%) for breast recurrence after SLN biopsy or axillary lymph node dissection (ALND); 7 (22%) after a recent, failed SLN biopsy or inadequate ALND; and 3 (9%) after earlier axillary surgery for an unrelated condition. RESULTS: SLNs were identified in 24 of 32 (75%) cases and were positive in 3 of 24 (13%). Reoperative SLN biopsy was more successful when less than 10 versus 10 or more nodes had been removed previously (87% versus 44%). Both blue dye and isotope identified the SLN in 16 of 24 successful procedures (67%). Additional, nonsentinel nodes (mean, eight nodes) were removed in 17 of 24 patients (71%) and were negative in all cases. At a median followup of 13 months, no axillary recurrences have occurred. CONCLUSIONS: Reoperative SLN biopsy after earlier SLN biopsy or ALND is feasible in selected breast cancer patients and is more likely to succeed when fewer than 10 nodes were removed during the earlier procedure. Further study is required to better define the subset of patients in whom reoperative SLN biopsy can replace ALND.

Number of lymph nodes removed in sentinel lymph node-negative breast cancer patients is significantly related to patient age and tumor size: a new source of bias in morbidity assessment?

BACKGROUND: Sentinel lymph node (SLN) biopsy has been well-established for axillary lymph node staging for patients with breast cancer. For lymph node-negative patients, planned "backup" axillary lymph node dissection (ALND) is rarely indicated. Among patients with negative SLNs, the authors observed variation by tumor size and patient age in the total number of lymph nodes removed (SLNs plus non-SLNs). They hypothesized that this variation is an unrecognized source of bias for studies examining the morbidity of SLN biopsy. METHODS: Retrospective review of this institution's SLN database identified 4103 SLN biopsy procedures between 1997 and 2004 in which SLN biopsy was performed for prophylactic mastectomy, ductal carcinoma in situ, or T1 to T2 invasive cancers, and the SLNs were benign. RESULTS: The mean number of SLNs, non-SLNs, and total lymph nodes for all tumor sizes was 2.8, 1.5, and 4.3, respectively, and increased with tumor size (more lymph nodes were removed for T2 than for T1 tumors: 6.3 vs 4.3; P < .0001). This trend remained significant even in the later years of these investigators' experience with SLN biopsy, and was observed for 5 of 9 (56%) surgeons. More total lymph nodes were also removed in patients aged 50 years (4.6 lymph nodes vs 4.2 lymph nodes; P = .006). In approximately 8% of patients (322 of 4103 patients), >or=10 lymph nodes were removed. CONCLUSIONS: The morbidity of SLN biopsy is less than that of ALND, but for pN0 patients, the total number of lymph nodes removed increased with tumor size and younger patient age. This variation is a previously unrecognized source of bias for studies that examine the morbidity of SLN biopsy.

Sentinel lymph node biopsy is successful and accurate in male breast carcinoma.

BACKGROUND: Men and women with breast cancer have similar risks of morbidity related to axillary lymph node dissection (ALND). Sentinel lymph node (SLN) biopsy minimizes this risk. We report results from the largest series of SLN biopsies for male breast cancer and compare this experience with that of female counterparts treated concurrently. STUDY DESIGN: The Memorial Sloan-Kettering Cancer Center SLN biopsy database showed that 7,315 SLN biopsy procedures were performed for primary breast cancer from September 1996 to July 2005. Of these, 78 (1.0%) procedures were performed in men. Followup data were obtained from medical record review. RESULTS: SLN biopsy was successful in 76 of 78 (97%) patients. Negative SLNs were found in 39 of 76 (51%) patients. In 3 (8%) patients with negative SLNs, a positive non-SLN was found, identified by intraoperative palpation. Positive SLNs were found in 37 of 76 (49%) patients. In 22 of 37 (59%), node positivity was determined intraoperatively, prompting immediate ALND. In 15 of 37 (41%) patients with positive SLNs, node positivity was determined postoperatively. Of these 15, 9 (60%) underwent completion ALND. In the 2 of 78 (3%) patients with failed SLN biopsy procedures, ALND was performed and yielded positive nodes. At a median followup of 28 months (range 5 to 96 months), there were no axillary recurrences. Compared with their female counterparts, men with breast cancer had larger tumors and were more likely to have positive nodes. CONCLUSIONS: SLN biopsy is successful and accurate in male breast cancer patients. Although a larger proportion of men have positive nodes, for men with negative nodes, SLN biopsy may reduce morbidity related to ALND.

Reoperative sentinel lymph node biopsy: a new frontier in the management of ipsilateral breast tumor recurrence.

BACKGROUND: Breast conservation therapy (BCT) with sentinel lymph node (SLN) biopsy is a well-established standard of care for primary operable breast cancer; 5-10% of BCT patients will develop local recurrence (LR). The question then arises: How best to manage the axilla in the setting of LR after previous BCT and SLN biopsy or axillary dissection (ALND)? METHODS: Between 9/96 and 12/04, 117 reoperative SLN were performed for LR after BCT and either SLN biopsy or ALND more than 6 months previously. Because of wide variation in the number of nodes removed at the initial procedure, validation by backup ALND was not feasible in all cases. RESULTS: Reoperative SLN was successful in 64/117 (55%) patients. SLNs were identified by isotope and dye in 28/64 (44%); isotope only in 29/64 (45%); dye only in 4/64 (6%); 3/64 (5%) unknown. Positive reoperative SLN were found in 10/64 (16%) successful cases. Among 54/64 (84%) patients with negative reoperative SLNs, 23 (43%) had additional non-SLN removed concurrently: these were negative in 21/23 cases (91%). In 2/23 (9%), reoperative SLN were falsely negative: one with a positive intramammary node, and the other with a positive non-SLN palpated at surgery. Success of reoperative SLN was inversely related to number of nodes removed previously, and was more likely to be successful after a previous SLN biopsy than a previous ALND (74% vs. 38%, P = 0.0002). Non-axillary drainage was identified by lymphoscintigraphy significantly more often in reoperative SLN than in primary SLN biopsy (30% vs. 6%, P < 0.0001). There were no local or axillary recurrences at a mean follow up of 2.2 years; 6 patients developed systemic recurrence. CONCLUSIONS: Reoperative SLN biopsy is feasible in the setting of LR after previous BCT/axillary surgery and deserves further study in this increasingly common clinical scenario. The added benefit of lymphoscintigraphy in identifying sites of non-axillary drainage may be greater in the setting of reoperative SLN than for the initial SLN procedure.

Results of MRI screening for breast cancer in high-risk patients with LCIS and atypical hyperplasia.

BACKGROUND: Magnetic resonance imaging (MRI) can detect breast cancer in high-risk patients, but is associated with a significant false-positive rate resulting in unnecessary breast biopsies. More data are needed to define the role of MRI screening for specific high-risk groups. We describe our experience with MRI screening in patients with atypical hyperplasia (AH) and lobular carcinoma in situ (LCIS). METHODS: We retrospectively reviewed data from our high-risk screening program prospective database for the period from April 1999 (when screening MRI was first performed at our institution) to July 2005. Patients with AH or LCIS demonstrated on previous surgical biopsy were identified. All patients underwent yearly mammography and twice yearly clinical breast examination. Additional screening MRI was performed at the discretion of the physician and patient. RESULTS: We identified 378 patients; 126 had AH and 252 had LCIS. Of these, 182 (48%) underwent one or more screening MRIs (mean, 2.6 MRIs; range, 1-8) during this period, whereas 196 (52%) did not. Those who had MRIs were younger (P < 0.001) with stronger family histories of breast cancer (P = 0.02). In MRI-screened patients, 55 biopsies were recommended in 46/182 (25%) patients, with 46/55 (84%) biopsies based on MRI findings alone. Cancer was detected in 6/46 (13%) MRI-generated biopsies. None of the six cancers detected on MRI were seen on recent mammogram. All six cancers were detected in five patients (one with bilateral breast cancer) with LCIS; none were detected by MRI in the AH group. Thus, cancer was detected in 5/135 (4%) of patients with LCIS undergoing MRI. The yield of MRI screening overall was cancer detection in 6/46 (13%) biopsies, 5/182 (3%) MRI-screened patients and 5/478 (1%) total MRIs done. In two additional MRI-screened patients, cancer was detected by a palpable mass in one, and on prophylactic surgery in the other and missed by all recent imaging studies. For 196 non-MRI-screened patients, 21 (11%) underwent 22 biopsies during the same period. Eight of 22 (36%) biopsies yielded cancer in seven patients. All MRI-detected cancers were stage 0-I, whereas all non-MRI cancers were stage I-II. CONCLUSION: Patients with AH and LCIS selected to undergo MRI screening were younger with stronger family histories of breast cancer. MRI screening generated more biopsies for a large proportion of patients, and facilitated detection of cancer in only a small highly selected group of patients with LCIS.

18F-2-fluoro-2-deoxy-D-glucose positron emission tomography scanning affects surgical management in selected patients with high-risk, operable breast carcinoma.

BACKGROUND: The role of positron emission tomography (PET) scanning in determining the extent of disease in patients with breast cancer has not been defined. We investigated the utility of (18)F-2-fluoro-2-deoxy-D: -glucose (FDG)-PET scanning compared with conventional imaging with computed tomographic scanning and bone scanning in determining the extent of disease in patients with high-risk, operable breast cancer. METHODS: This was a prospective study of patients who presented to Memorial Sloan-Kettering Cancer Center for operative treatment of breast cancer. Eighty eligible patients were enrolled and underwent computed tomographic chest, abdomen, pelvis, and bone scans, followed by FDG-PET. Changes in treatment based on scan findings were recorded by the operating surgeons. Imaging findings were verified by biopsy or long-term follow-up. RESULTS: Eight (10%) of 80 patients were found to have metastatic disease that was seen on both conventional imaging and PET. Four additional patients (5%) had additional foci of disease on PET that affected treatment decisions. No patient had findings on conventional imaging alone. Conventional imaging studies resulted in a higher number of findings that generated additional tests and biopsies that ultimately had negative results (17% vs. 5% for PET). There was a statistically significant difference in specificity for PET compared with conventional imaging (P = .01). CONCLUSIONS: Conventional imaging and PET were equally sensitive in detecting metastatic disease in patients with high-risk, operable breast cancer, but PET generated fewer false-positive results. FDG-PET scanning should be further studied in this setting and considered in the preoperative evaluation of selected patients with breast cancer.

A prospective analysis of the effect of blue-dye volume on sentinel lymph node mapping success and incidence of allergic reaction in patients with breast cancer.

BACKGROUND: This study examined whether the volume of isosulfan blue dye used in sentinel lymph node (SLN) mapping in breast cancer is related to the SLN identification rate or to the incidence of allergic reactions. METHODS: From January 2001 to November 2002, 1728 breast cancer patients underwent 1832 SLN mapping procedures with the combined technique of intraparenchymal blue dye and intradermal radioisotope. Details of each procedure and all allergic reactions were prospectively recorded. Bilateral synchronous SLN procedures were considered as one dye exposure but as two distinct procedures for determining mapping success. Dye-only success was defined as the proportion of cases in which the SLN was identified by blue dye alone. Overall dye success was defined as the proportion of cases in which the SLN was identified by blue dye with or without isotope. RESULTS: When stratified by volume of blue dye, there were no significant differences in dye-only successes, overall dye successes, or mapping failures. Allergic reactions were documented in 31 (1.8%) of 1728 patients. Hypotensive reactions occurred in 3 (.2%) of 1728 patients; 2 (.1%) required pressor support. There was a nonsignificant trend toward fewer allergic reactions with smaller volumes of blue dye. CONCLUSIONS: In combined-technique SLN mapping protocols for breast cancer, using smaller volumes of blue dye may represent a means of optimizing the safety of the procedure without compromising its success.