Jeanne A. Petrek

The Risk of Axillary Relapse After Sentinel Lymph Node Biopsy for Breast Cancer Is Comparable With That of Axillary Lymph Node Dissection: A Follow-up Study of 4008 Procedures

Objective:We sought to identify the rate of axillary recurrence after sentinel lymph node (SLN) biopsy for breast cancer. Summary Background Data:SLN biopsy is a new standard of care for axillary lymph node staging in breast cancer. Nevertheless, most validated series of SLN biopsy confirm that the SLN is falsely negative in 5–10% of node-positive cases, and few studies report the rate of axillary local recurrence (LR) for that subset of patients staged by SLN biopsy alone. Methods:Through December of 2002, 4008 consecutive SLN biopsy procedures were performed at Memorial Sloan-Kettering Cancer Center for unilateral invasive breast cancer. Patients were categorized in 4 groups: SLN-negative with axillary lymph node dissection (ALND; n = 326), SLN-negative without ALND (n = 2340), SLN-positive with ALND (n = 1132), and SLN-positive without ALND (n = 210). Clinical and pathologic characteristics and follow-up data for each of the 4 cohorts were evaluated with emphasis on patterns of axillary LR. Results:With a median follow-up of 31 months (range, 1–75), axillary LR occurred in 10/4008 (0.25%) patients overall. In 3 cases (0.07%) the axillary LR was the first site of treatment failure, in 4 (0.1%) it was coincident with breast LR, and in 3 (0.07%) it was coincident with distant metastases. Axillary LR was more frequent among the unconventionally treated SLN-positive/no ALND patients than in the other 3 conventionally treated cohorts (1.4% versus 0.18%, P = 0.013). Conclusions:Axillary LR after SLN biopsy, with or without ALND, is a rare event, and this low relapse rate supports wider use of SLN biopsy for breast cancer staging. There is a low-risk subset of SLN-positive patients in whom completion ALND may not be required.

Sentinel lymph node biopsy: is it indicated in patients with high-risk ductal carcinoma-in-situ and ductal carcinoma-in-situ with microinvasion?

Background: Axillary lymph node status is the strongest prognostic indicator of survival for women with breast cancer. The purpose of this study was to determine the incidence of sentinel node metastases in patients with high-risk ductal carcinoma-in-situ (DCIS) and DCIS with microinvasion (DCISM).Methods: From November 1997 to November 1999, all patients who underwent sentinel node biopsy for high-risk DCIS (n = 76) or DCISM (n = 31) were enrolled prospectively in our database. Patients with DCIS were considered high risk and were selected for sentinel lymph node biopsy if there was concern that an invasive component would be identified in the specimen obtained during the definitive surgery. Patients underwent intraoperative mapping that used both blue dye and radionuclide. Excised sentinel nodes were serially sectioned and were examined by hematoxylin and eosin and by immunohistochemistry.Results: Of 76 patients with high-risk DCIS, 9 (12%) had positive sentinel nodes; 7 of 9 patients were positive for micrometastases only. Of 31 patients with DCISM, 3 (10%) had positive sentinel nodes; 2 of 3 were positive for micrometastases only. Six of nine patients with DCIS and three of three with DCISM and positive sentinel nodes had completion axillary dissection; one patient with DCIS had an additional positive node detected by conventional histological analysis.Conclusions: This study documents a high incidence of lymph node micrometastases as detected by sentinel node biopsy in patients with high-risk DCIS and DCISM. Although the biological significance of breast cancer micrometastases remains unclear at this time, these findings suggest that sentinel node biopsy should be considered in patients with high-risk DCIS and DCISM.

Incidence, Time Course, and Determinants of Menstrual Bleeding After Breast Cancer Treatment: A Prospective Study

PURPOSE To assess ovarian function using the surrogate of monthly bleeding after breast cancer treatment in premenopausal women. PATIENTS AND METHODS Five hundred ninety-five US women age 20 to 45 years were accrued from January 1998 to July 2002 within 8 months of diagnosis with stages I to III breast cancer (median follow-up 45 months). Daily bleeding records were obtained prospectively, as well as extensive clinical, demographic, quality of life, and treatment data. Repeated measures logistic regression was used to assess which variables were predictive of monthly bleeding. RESULTS Significantly different proportions of women had monthly bleeding depending on their age (P < .001), chemotherapy program (P < .001), and time since treatment regimen. In the month after the standard course of doxorubicin and cyclophosphamide (AC), whether or not followed by paclitaxel or docetaxel, approximately 16% had monthly bleeding compared with the cyclophosphamide, methotrexate, fluorouracil (CMF) group, in which 48% bled (P < .001). Following any AC regimen, there was a slow recovery phase of about 9 months followed by a plateau, during which almost half continued monthly bleeding for the remainder of the follow-up period compared with after CMF in which there was no recovery phase and a continual decline in monthly bleeding to approximately 18% of women at study end (P < .001). Tamoxifen use decreased bleeding between months 12 and 24 after chemotherapy with 15% fewer women having bleeding. CONCLUSION Using daily menstrual bleeding records, it is demonstrated that age, the specific chemotherapy regimen received, and tamoxifen use impact ovarian function.

Lymphedema: Current issues in research and management

Lymphedema is a common and troublesome problem that can develop following breast cancer treatment. As with other quality‐of‐life and nonlethal conditions, it receives less research funding and attention than do many other areas of study.

Prognosis of pregnancy-associated breast cancer

The survival of patients with pregnancy‐associated (PA) breast cancer is difficult to predict for two reasons: The combination is very rare, and the natural history of breast cancer that is not associated with pregnancy is intricate and varies among individuals. Valid data collection and analysis is problematic given that studies gather patients over many years. The charts of 56 women with Stages I, II, and III breast cancer, who were pregnant or within 1 year postpartum at the time of breast cancer diagnosis between 1960 and 1980, were analyzed. Patients with PA breast cancer were compared to nonpregnant women of comparable ages, who were treated at the same hospital, by the same physicians, and during the same period. Four patients were lost before 5‐year follow‐up, and one patient before 10‐year follow‐up. These five patients had distant metastases at the time they were lost to follow‐up, and are considered to have died within that time. Across stages, patients with PA breast cancer have survival not significantly different from those patients with non‐pregnancy‐associated (non‐PA) breast cancer.

Breast Cancer in Patients Irradiated for Hodgkin's Disease: A Clinical and Pathologic Analysis of 45 Events in 37 Patients

PURPOSE To characterize the clinical and pathologic features of patients who developed breast cancer (BC) after treatment for Hodgkins disease (HD). Recent epidemiologic studies have shown that women who are cured of HD have an increased risk of developing BC. PATIENTS AND METHODS The clinical data, mammograms, and pathologic specimens of 37 women who developed 45 BCs (eight bilateral events), and had a prior history of treatment for HD were analyzed. RESULTS The median age at diagnosis of HD was 27 years (range, 11 to 60). All patients received radiotherapy (RT) to the upper part of their body, and 10 also had chemotherapy for HD. The median interval from the treatment of HD to the diagnosis of BC was 15 years (range, 8 to 34). The median age at diagnosis of BC was 43 years (range, 27 to 75), 41% of patients were 39 years old or younger. Most mammograms (81%) showed abnormal findings of mass and/or microcalcifications. Of the eight patients (22%) with bilateral tumors, four were synchronous and four were metachronous. Involvement of the medial half of the breast occurred more frequently than in patients with primary BC (39% and 21%, respectively; P < .002). But, the histologic types, grades, presence of lymphocytic reaction, and lymphatic invasion were similar to those observed in 935 primary BC patients who were previously analyzed at our center. The 6-year actuarial relapse-free survival (RFS) for node-negative BC after HD was 85%. Node-positive patients had a significantly lower RFS of 33% (P = .002). CONCLUSIONS In comparison to patients with primary BC, patients who develop BC after HD are more likely to be younger, have bilateral disease, and have their tumors more frequently involve the medial half of the breast. Pathologic characteristics, nodal involvement, and prognosis are similar to those of primary BC. BC in women who were treated for HD is becoming an increasing problem, as more patients cured of HD reach a follow-up time of 10 to 15 years. Breast examination and mammography at an early age should be part of the follow-up program for women who are cured of HD.

Isosulfan blue dye reactions during sentinel lymph node mapping for breast cancer

UNLABELLED In the United States, identification of the sentinel lymph node (SLN) requires the use of (99m)Tc-labeled colloid, 1% isosulfan blue dye, or both to trace the lymphatic drainage of a given neoplasm. We report our experience with adverse reactions to isosulfan blue dye during SLN mapping in breast cancer. A chart review of the breast cancer SLN database was performed; it included 2392 sequential patients who underwent SLN biopsy involving isosulfan blue dye at Memorial Sloan-Kettering Cancer Center from September 12, 1996, to August 17, 2000. Thirty-nine of 2392 patients (1.6%) had a documented allergic reaction during the mapping procedure. Most reactions (69%) produced urticaria, blue hives, a generalized rash, or pruritus. The incidence of hypotensive reactions was 0.5%. Although anaphylaxis after the injection of isosulfan blue dye is rare, this article highlights the need to suspect anaphylaxis when hemodynamic instability occurs after the injection of this compound. Our experience indicates that bronchospasm and respiratory compromise are unusual and that most patients do not require emergent intubation and can be managed with short-term pressor support. In addition, our data indicate that patients with a sulfa allergy do not display a cross-sensitivity to isosulfan blue dye. IMPLICATIONS We report the largest single-institution review of adverse reactions to injection of isosulfan blue dye during sentinel lymph node mapping in breast cancer. Bronchospasm and respiratory compromise are unusual, and most patients can be treated with short-term pressor support. Patients with a sulfa allergy do not display a cross-sensitivity to isosulfan blue dye.

A trend analysis of the relative value of blue dye and isotope localization in 2,000 consecutive cases of sentinel node biopsy for breast cancer.

BACKGROUND Among the advocates of blue dye, isotope, or combined dye-isotope mapping of the sentinel lymph node (SLN) for breast cancer, there is no universal consensus as to which technique is optimal and whether the relative value of each method changes with increasing experience. The objective of this study was to examine the relative contributions of blue dye and radioisotope to successful identification of the SLN as the SLN-mapping technique evolved over our first 2,000 consecutive cases. STUDY DESIGN Using the first 2,000 consecutive SLN biopsy procedures for breast cancer, performed by eight surgeons (none previously experienced in SLN techniques) at one institution, using a combined technique of blue dye and isotope mapping, we report the institutional learning curve and the relative contributions of dye and isotope to identifying both the SLN and the positive SLN, by increments of 500 cases. RESULTS Comparing the first 500 with the most recent 500 cases, success in identifying the SLN by blue dye did not improve with experience, although success in isotope localization steadily increased, from 86% to 94% (p < 0.00005). With the increasing success of isotope mapping, the marginal benefit of blue dye (the proportion of cases in which the SLN was identified by blue dye alone) steadily declined, from 9% to 3% (p = 0.0001). Parallel to this trend, the proportion of positive SLNs identified by blue dye did not change with experience (89% to 90%), but isotope success steadily increased, from 88% to 98% (p = 0.0015). The proportion of positive SLNs identified by blue dye alone declined from 12% to 2% (p = 0.0015). CONCLUSIONS Using a combined technique of blue dye and radioisotope mapping, and with refinement of the radioisotope technique, we report 97% success identifying the SLN. Although we continue to recommend the use of both methods in SLN mapping for breast cancer, we observe with experience a declining marginal benefit for blue dye.

Sensory morbidity after sentinel lymph node biopsy and axillary dissection: a prospective study of 233 women.

BackgroundWe prospectively compared the sensory morbidity and lymphedema experienced after sentinel node biopsy (SLNB) and axillary dissection (ALND) over a 12-month period by using a validated instrument.MethodsPatients undergoing breast-conserving therapy completed the Breast Sensation Assessment Scale (BSAS) at baseline and 3, 6, and 12 months after surgery. Repeated-measures analysis of variance was used to compare ALND and SLNB over the 12-month period. Upper- and lower-arm circumference measurements at baseline and 12 months were used to assess lymphedema.ResultsSLNB was associated with substantial sensory morbidity, although significantly less than ALND, over time on all four subscales and the summary score. A statistically significant improvement in sensory morbidity occurred for both groups in the first 3 months, with no further change thereafter. For both types of axillary surgery, younger patients had significantly higher BSAS scores than older patients. There was no significant difference in arm circumference between patients with SLNB and ALND at 12 months.ConclusionsAmong women undergoing breast-conserving therapy, SLNB has significant sensory morbidity, although approximately half that of ALND. Sensory morbidity improves in the first 3 months after surgery, but patients continue to report sensory morbidity at 1 year. Longitudinal follow-up is required to further assess lymphedema.

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.