Nonsurgical ablation of breast cancer: future options for small breast tumors.

The surgical management of breast cancer has evolved significantly, facilitated by advancements in technology and imaging and improvements in adjuvant therapy. The changes in surgical management have been characterized by equal or improved outcomes with significantly less morbidity. The next step in this evolution is the minimally invasive or noninvasive ablation of breast cancers as an alternative to lumpectomy. In this article, the various modalities for nonsurgical breast cancer ablation and the clinical experience are reviewed, and some of the next steps necessary for their clinical implementation are outlined.

Obesity and angiolymphatic invasion in primary breast cancer.

BACKGROUND: Obesity is associated with poorer breast cancer-specific survival. The purpose of this study was to investigate the relationships between obesity and the presence of angiolymphatic invasion as well as other features of invasive breast cancer, including stage at presentation, estrogen receptor (ER) status, triple-negative phenotype, and tumor grade. METHODS: Detailed clinical and pathologic data were abstracted from the medical records of all 1,312 patients with stage I-III primary breast cancer who had breast surgery at the University of Michigan Comprehensive Cancer Center between January 1, 2000 and December 31, 2006. Bivariate and multivariate analyses were conducted to investigate the relationships between body mass index and tumor biologic features, controlling for menopausal status, diabetes and hypertension, hormone replacement therapy before diagnosis, race, and ethnicity. RESULTS: In multivariate analyses, severe obesity was independently associated with the presence of angiolymphatic invasion [odds ratio (OR) 1.80, 95% confidence interval (CI) 1.08-2.99, joint test of significance, P = 0.03]. Severe obesity was associated with lower likelihood of triple-negative breast cancer (OR 0.39, 95% CI 0.16-0.96). Among premenopausal women with diabetes, ER-negative (OR 5.22, 95% CI 1.12-24.29) and triple-negative (OR 14.8, 95% CI 1.92-113.91) disease was significantly more common. DISCUSSION: In this large sample of invasive breast cancers, obesity was independently associated with the presence of angiolymphatic invasion. Higher rates of angiolymphatic invasion among obese women may account in part for poorer outcomes among obese women with breast cancer.

Determinants of breast conservation rates: reasons for mastectomy at a comprehensive cancer center.

Bias in referral patterns and variations in multi-disciplinary management may impact breast conservation therapy (BCT) rates between hospitals. Retrospective studies of BCT rates are limited by their inability to differentiate indicated mastectomies versus those chosen by the patient. Our prospective breast cancer data base was queried for patients with invasive breast cancer who underwent surgical therapy at the University of Michigan over a 3-year period. Demographics, stage and histology were recorded along with the reason mastectomy was performed, categorized as "by need" (contraindication to BCT) or "by choice." Multivariate analysis was used to identify factors significantly associated with mastectomy by choice. BCT was associated with tumor size, histology and nodal status, but not older age, either by choice or by need. Of the 34% of patients initially felt to be poor candidates for BCT, it was absolutely contraindicated in 44%, while 56% were thought to have a tumor-to-breast size ratio too large for successful BCT. Of this latter group, 80% underwent neo-adjuvant chemotherapy in an attempt to downstage the primary tumor and perform BCT, which was successful in over half the patients. For the patients initially thought to be good candidates for BCT, only 15% chose to undergo mastectomy, while 5% eventually required mastectomy due to failed attempts to achieve negative margins. Overall, the BCT rate was 63%, however without the use of neo-adjuvant chemotherapy, the BCT rate would have been only 53%. At a tertiary referral center, BCT rates are driven more by contraindications than patient choice, and may be heavily skewed towards mastectomy due to referral patterns. In addition to tumor factors such as stage and histology, BCT rate can be dramatically impacted by neo-adjuvant chemotherapy or genetic counseling. Examining BCT rates alone as a measure of quality, therefore, is not an appropriate standard across institutions serving diverse populations.

Sentinel lymph node biopsy performed after neoadjuvant chemotherapy is accurate in patients with documented node-positive breast cancer at presentation.

BACKGROUND: The optimal strategy for incorporating lymphatic mapping and sentinel lymph node biopsy into the management of breast cancer patients receiving neoadjuvant chemotherapy remains controversial. Previous studies of sentinel node biopsy performed following neoadjuvant chemotherapy have largely reported on patients whose prechemotherapy, pathologic axillary nodal status was unknown. We report findings using a novel comprehensive approach to axillary management of node-positive-patients receiving neoadjuvant chemotherapy. METHODS: We evaluated 54 consecutive breast cancer patients with biopsy-proven axillary nodal metastases at the time of diagnosis that underwent lymphatic mapping with nodal biopsy as well as concomitant axillary lymph node dissection after receiving neoadjuvant chemotherapy. All cases were treated at a single comprehensive cancer center between 2001 and 2005. RESULTS: The sentinel node identification rate after delivery of neoadjuvant chemotherapy was 98%. Thirty-six patients (66%) had residual axillary metastases (including eight patients that had undergone resection of metastatic sentinel nodes at the time of diagnosis), and in 12 cases (31%) the residual metastatic disease was limited to the sentinel lymph node. The final, post-neoadjuvant chemotherapy sentinel node was falsely negative in three cases (8.6%). The negative final sentinel node accurately identified patients with no residual axillary disease in 17 cases (32%). CONCLUSIONS: Sentinel lymph node biopsy performed after the delivery of neoadjuvant chemotherapy in patients with documented nodal disease at presentation accurately identified cases that may have been downstaged to node-negative status and can spare this subset of patients (32%) from experiencing the morbidity of an axillary dissection.

Significance of multiple lymphatic basin drainage in truncal melanoma patients undergoing sentinel lymph node biopsy.

BACKGROUND: Truncal melanoma involving metastases to multiple lymph node basins has a much worse prognosis than tumor involvement of a single lymph node basin. Recent results also suggest that, independently of the status of lymph node involvement, patients with multiple lymphatic basin drainage (MLBD) on lymphoscintigraphy have an increased risk of lymph node metastasis and a worse prognosis than those with a single lymphatic drainage basin. Because published reports have conflicting results, the authors compared their experience at the University of Michigan Comprehensive Cancer Center with recently published findings. METHODS: The authors searched a prospectively maintained melanoma database at the University of Michigan for patients with primary truncal melanoma who underwent lymphoscintigraphy and sentinel lymph node biopsy between 1997 and 2004. The association of MLBD with the clinical and pathologic characteristics collected and the presence of regional metastases was tested by using contingency tables and the chi(2) test statistic and by using the Fisher's exact test statistic when cell frequencies were small. The product-limit method of Kaplan and Meier was used to estimate disease-free and overall survival probabilities. RESULTS: Of 423 patients with primary truncal melanoma who underwent sentinel lymph node biopsy, 123 (29%) had a positive result, and 98 patients (23.2%) had MLBD. Patients with tumors located in the middle of the trunk and tumor ulceration were more likely to have MLBD (P < .0001 and P = .045, respectively). Patients with a single lymphatic drainage basin and MLBD had a similar risk of lymph node metastasis and similar disease-free and overall survival. CONCLUSIONS: Patients with truncal melanomas tend to have MLBD when the tumor is located in the middle of the trunk or when ulceration is present. In our experience, drainage to multiple lymphatic basins was not an independent risk factor for sentinel lymph node metastasis and has no independent prognostic significance.

Lymphatic mapping and sentinel lymph node biopsy for patients with local recurrence after breast-conservation therapy.

BACKGROUND: Local recurrence (LR) after breast-conservation therapy for breast cancer occurs in 10% to 15% of cases. A subset of these represents biologically aggressive disease, yet prognostic features for identifying this high-risk category are lacking. We hypothesized that lymphatic mapping and sentinel lymph node biopsy would provide useful information regarding dominant lymphatic drainage patterns of patients with LR. METHODS: Breast cancer case records involving surgery for LR at the University of Michigan from 2002 to 2004 were reviewed. The lymphatic drainage patterns were compared with those of 117 patients who underwent mapping for primary breast cancer. RESULTS: Fourteen LR cases were identified (10 with initial axillary lymph node dissection, 2 with initial sentinel lymph nodes, and 2 with no axillary surgery at the time of primary cancer treatment); lymphatic mapping was performed in 10. The sentinel lymph node identification rate was 90%, the median number of lymph nodes retrieved was 3, and no metastases were detected. Significantly more cases of nonipsilateral axillary sentinel node drainage were observed in mapping procedures performed for LR compared with those for primary breast cancer (67% vs. 15%; P = .001). CONCLUSIONS: Lymphatic mapping is feasible in patients undergoing mastectomy for LR and is likely to identify aberrantly located sentinel lymph nodes that would otherwise be overlooked with a conventional completion mastectomy.

Clinicopathologic features associated with having four or more metastatic axillary nodes in breast cancer patients with a positive sentinel lymph node.

BACKGROUND: The survival benefit of a completion axillary lymph node dissection (ALND) in patients after removal of a metastatic sentinel lymph node (SLN) is uncertain and is under study in ongoing clinical trials. The completion ALND remains necessary, however, for the identification of cases with at least four metastatic lymph nodes, in which extended-field locoregional and/or postmastectomy radiation will be recommended. Our goal was evaluate clinicopathologic features that might serve as surrogates for determining which patients with a positive SLN are likely or unlikely to belong to this high-risk subset. METHODS: Records were reviewed for 285 patients from 2 comprehensive cancer centers who underwent completion ALND after resection of a metastatic SLN from 1995 to 2002. Clinicopathologic features were analyzed by univariate and multivariate logistic regression. Forty-one cases (14%) were found to have at least four positive nodes after ALND. RESULTS: Fisher's exact test revealed the following features to be significantly (P < .05) associated with having four or more nodal metastases: tumor size >2 cm, lymphovascular invasion, an increasing ratio of positive SLNs to the total number of resected SLNs, extranodal extension, and the size of the SLN metastasis. Patients whose largest SLN metastasis was <2 mm had only a 1.4% risk of having four or more metastatic nodes (P < .0001). CONCLUSIONS: We conclude that patients with SLN micrometastases face an extremely low likelihood of having extensive nodal disease on completion ALND. Patients with larger primary tumors, lymphovascular invasion, and extranodal extension are more likely to have ALND findings that will affect their cancer management.

Comprehensive axillary evaluation in neoadjuvant chemotherapy patients with ultrasonography and sentinel lymph node biopsy.

BACKGROUND: There is ongoing debate regarding the optimal sequence of sentinel lymph node (SLN) biopsy and neoadjuvant chemotherapy (CTX) for breast cancer. We report the accuracy of comprehensive pre-neoadjuvant CTX and post-neoadjuvant CTX axillary staging via ultrasound imaging, fine-needle aspiration (FNA) biopsy, and SLN biopsy. METHODS: From 2001 to 2004, 91 neoadjuvant CTX patients at the University of Michigan Comprehensive Cancer Center underwent axillary staging by ultrasonography, ultrasound-guided FNA biopsy, SLN biopsy, or a combination of these. RESULTS: Axillary staging was pathologically negative by pre-neoadjuvant CTX SLN biopsy in 53 cases (58%); these patients had no further axillary surgery. In 38 cases (42%), axillary metastases were confirmed at presentation by either ultrasound-guided FNA or SLN biopsy. These 38 patients underwent completion axillary lymph node dissection (ALND) after delivery of neoadjuvant CTX. Follow-up lymphatic mapping was attempted in 33 of these cases, and the SLN was identified in 32 (identification rate, 97%). One third of these cases were completely node negative on ALND. Residual metastatic disease was identified in 22 cases, and the SLN was falsely negative in 1 (4.5%). CONCLUSIONS: Patients receiving neoadjuvant CTX can have accurate axillary nodal staging by ultrasound-guided FNA or SLN biopsy. In cases of documented axillary metastasis at presentation, repeat axillary staging with SLN biopsy can document the post-neoadjuvant CTX nodal status. This strategy optimizes pre-neoadjuvant CTX and post-neoadjuvant CTX staging information by distinguishing the patients who are node negative at presentation from those who have been downstaged to node negativity and offers the potential for avoiding unnecessary ALNDs in both of these patient subsets.