Omission of radiotherapy after breast conservation surgery in the postneoadjuvant setting.

BACKGROUND: Breast conservation therapy (BCT) consists of breast conservation surgery (BCS) and radiotherapy (RT). Neoadjuvant chemotherapy (NACT) can downstage tumors, broadening BCS eligibility in patients requiring mastectomy. However, tumor downstaging does not obviate need for RT. This study evaluated factors that predict RT omission after NACT and BCS. METHODS: The National Cancer Database was queried for women with unilateral, clinical stage II-III breast cancer, treated with NACT and BCS between 2008 and 2012. Patients not receiving RT after NACT and BCS were identified. A subgroup analysis was performed eliminating patients for whom RT was recommended but not received. RESULTS: Among 10,220 patients meeting study eligibility, 974 (9.53%) did not receive RT after BCS. Predictors of RT omission included older age, insurance status, facility type, facility region, more recent year of diagnosis, receptor status unknown, human epidermal growth factor receptor 2 status positive or unknown, and positive margins. Factors increasing the likelihood of RT receipt included cN3 disease, receptor positivity, and primary downstaging. Race, Hispanicity, education, income, comorbidities, rural versus urban setting, histology, grade, and nodal stage change were not associated with RT omission. When excluding the 314 patients for whom RT was recommended but not received, age, Medicaid insurance, facility type, facility region, receptor status unknown, human epidermal growth factor receptor 2 status unknown, and positive margins were predictors of RT omission. CONCLUSIONS: Race, comorbidities, and socioeconomic status were not predictors of RT omission. It remains unclear whether omission of RT in some cases is due to lack of physician knowledge. Further efforts are needed to ensure that physicians and patients recognize that RT is a vital and required part of BCT, even after NACT.

Breast conservation versus mastectomy for patients with T3 primary tumors (>5 cm): A review of 5685 medicare patients.

BACKGROUND: Although breast conservation therapy (BCT) is standard for breast cancer treatment, patients with tumors measuring >5 cm have been excluded from clinical trials. Nevertheless, only a few small retrospective series to date have compared BCT with mastectomy for tumors measuring >5 cm. The current study was performed to determine whether survival is equivalent for BCT versus mastectomy using a large national data set. METHODS: Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked cases were identified for patients aged ≥ 66 years undergoing breast conservation for invasive, noninflammatory, nonmetastatic breast cancer between 1992 and 2009. Propensity score-based adjustment was used to account for demographics and tumor and treatment factors. RESULTS: A total of 5685 patients with tumors measuring >5.0 cm underwent breast surgery, with 15.6% receiving BCT. Mean ages of the patients and tumor sizes were similar. Predictors of BCT included neoadjuvant chemotherapy and postoperative radiotherapy use, higher income, breast cancer as a first malignancy, and a higher Charlson Comorbidity Index. Predictors of mastectomy included younger age, nonductal histology, higher grade, numbers of lymph nodes examined and found to be positive, American Joint Committee on Cancer stage III disease, postoperative chemotherapy use, and residential region of the country. Adjusted overall and breast cancer-specific survival were not different between patients treated with BCT and mastectomy (hazard ratio, 0.934; 95% confidence interval, 0.791-1.103 [P = .419] for overall survival; and subdistribution hazard ratio, 1.042; 95% confidence interval, 0.793-1.369 [P = .769] for breast cancer-specific survival), with each improving over time. The median follow-up was 7.0 years. CONCLUSIONS: For Medicare patients with tumors measuring >5 cm, survival is similar between those treated with BCT and mastectomy as for patients with smaller primary tumors. Despite exclusion from randomized trials, BCT may remain an option for patients with larger tumors when deemed clinically and cosmetically amenable to surgical resection.

Multifocal and multicentric breast cancer is associated with increased local recurrence regardless of surgery type.

Multifocal and multicentric breast cancers have been correlated with poor prognostic factors and worse outcomes versus unifocal disease. We evaluated the impact of multifocal and multicentric disease versus case controls with unifocal disease, matching for age, grade, T-, and N-stage. A total of 110 patients with multifocal (n = 93) or multicentric (n = 17) disease and 263 matched case controls were identified with a median follow-up of 53 months and 64 months, respectively. The actuarial local control rates for the multifocal/multicentric and unifocal group were 88% and 97%, respectively at both 5 and 10 years (p < 0.001). On multivariate analysis, multifocal/multicentric disease remained associated with higher local recurrence after controlling for other covariates including surgery type. The disease-free survival rates in the multifocal/multicentric group at 5 and 10 years were 75% and 71%, respectively, versus 87% and 78% at 10 years (p = 0.01). On multivariate analysis, multifocal/multicentric disease was no longer associated with worse disease-free survival. There was no difference in the cohorts in terms of regional control, overall survival, or cancer specific survival. Our findings suggest that multifocal/multicentric disease may be associated with worse outcomes versus unifocal disease regardless of type of surgery. This suggests a more biologically aggressive cancer and may be an important consideration when managing these patients. Further studies are needed to better understand the impact of multifocal/multicentric breast cancers on outcomes.

Patterns of nodal staging during breast conservation surgery in the medicare patient: will the ACOSOG Z0011 trial change the pattern of care?

ACOSOG Z0011 spares axillary dissection (AD) in breast conservation surgery (BCS) patients with T1/T2 tumors and 1-2 positive nodes. Current patterns of care and the impact of Z0011 on AD versus additional surgery rates for Medicare patients undergoing BCS are unknown. SEER data linked to Medicare claims for 1999-2005 were reviewed for women with invasive nonmetastatic breast cancer who underwent nodal staging on the same day as BCS. There were 3,280 women with T1/T2 tumors and positive nodes who underwent same-day nodal staging; 2,532 (77.2 %) of these women had 1-2 positive nodes. Assuming 25.7 % have extracapsular extension, 651 women would require AD. However, 1,881 women, or 57.4 % of those with T1/T2 tumors and positive nodes, would be spared AD. Meanwhile, among the 748 women having ≥ 3 positive nodes, 579 underwent same-day AD, but under Z0011, would now wait for permanent section. A total of 160 of these women underwent re-excision or completion mastectomy at a later date anyway, when delayed AD could be performed. The remaining 419 women with ≥ 3 positive nodes would require an additional surgery date for the sole purpose of completion AD. The Z0011 paradigm would consequently necessitate an additional surgery date for 1,070 (651 + 419) women, or 32.6 % of those with T1/T2 tumors and positive nodes. The Z0011 paradigm appears to increase the number of Medicare patients undergoing BCS who require an additional surgery date but decrease the number requiring AD to a greater extent. Future changes in the use of AD or axillary irradiation may yet modify that impact substantially.

Advanced imaging modalities in early stage breast cancer: preoperative use in the United States Medicare population.

BACKGROUND: Guidelines for breast cancer staging exist, but adherence remains unknown. This study evaluates patterns of imaging in early stage breast cancer usually reserved for advanced disease. METHODS: Surveillance Epidemiology, and End Results data linked to Medicare claims from 1992-2005 were reviewed for stage I/II breast cancer patients. Claims were searched for preoperative performance of computed tomography (CT), positron emission tomography (PET), bone scans, and brain magnetic resonance imaging (MRI) ("advanced imaging"). RESULTS: There were 67,874 stage I/II breast cancer patients; 18.8% (n=12,740) had preoperative advanced imaging. The proportion of patients having CT scans, PET scans, and brain MRI increased from 5.7% to 12.4% (P<0.0001), 0.8% to 3.4% (P<0.0001) and 0.2% to 1.1% (P=0.008), respectively, from 1992 to 2005. Bone scans declined from 20.1% to 10.7% (P<0.0001). "Breast cancer" (174.x) was the only diagnosis code associated with 62.1% of PET scans, 37.7% of bone scans, 24.2% of CT, and 5.1% of brain MRI. One or more symptoms or metastatic site was suggested for 19.6% of bone scans, 13.0% of CT, 13.0% of PET, and 6.2% of brain MRI. Factors associated (P<0.05) with use of all modalities were urban setting, breast MRI and ultrasound. Breast MRI was the strongest predictor (P<0.0001) of bone scan (odds ratio [OR] 1.63, 95% confidence interval [CI] 1.44-1.86), Brain MRI (OR 1.74, 95% CI 1.15-2.63), CT (OR 2.42, 95% CI 2.12-2.76), and PET (OR 5.71, 95% CI 4.52-7.22). CONCLUSIONS: Aside from bone scans, performance of advanced imaging is increasing in early stage Medicare breast cancer patients, with limited rationale provided by coded diagnoses. In light of existing guidelines and increasing scrutiny about health care costs, greater reinforcement of current indications is warranted.

Method of primary tumor detection as a risk factor for local and distant recurrence after breast-conservation treatment for early-stage breast cancer.

BACKGROUND: Recent studies have shown that breast cancer detected by screening has a more favorable prognosis than interval breast cancer. To further understand the biologic significance of this finding, we investigated the association of disease recurrence, local and distant, with the method of detection of the primary breast cancer in a cohort of 1686 women treated with breast conservation. PATIENTS AND METHODS: The charts of 1686 women with primarily stage I or II invasive breast cancer treated by breast conservation between 1977 and 2002 were reviewed. The median length of follow-up was 6 years. Univariate and multivariate analyses using binary logistic regression were performed for 2 subgroups: (1) those with local recurrence versus those without; and (2) those with distant metastasis versus those without distant metastasis. RESULTS: Our data confirmed several of the well-known risk factors for local and distant recurrence. In addition, we found that individuals with breast cancer detected on physical examination alone have a significantly higher risk for local recurrence compared with patients with cancer detected on mammogram alone, independent of tumor size (odds ratio [OR], 2.369; 95% CI, 1.235-4.547; P = .01). We also found a similar correlation for risk of distant metastasis in these 2 groups of women (OR, 2.201; 95% CI, 1.211-3.998; P = .01). CONCLUSION: Breast cancers that are palpable might represent an aggressive biologic subtype with an increased risk of local and distant recurrence. Risk stratification might need to include this clinical feature in addition to conventional prognostic factors.

Mammographic appearance of recurrent breast cancer after breast conservation therapy.

RATIONALE AND OBJECTIVES: To compare the mammographic appearance of recurrent breast cancer to the primary tumor in patients treated with breast conservation therapy. MATERIALS AND METHODS: The charts of women with American Joint Committee on Cancer Stage I or II breast cancer who underwent breast conservation therapy between 1977 and 2001 at our institution were reviewed. A total of 132 patients were diagnosed with local recurrence. RESULTS: The mammographic appearance of the local recurrence often varied from the appearance of the original breast cancer. This was especially true for women who had mammographically occult primary breast cancer. In these women, the recurrence was detected mammographically 76.9% of the time. CONCLUSIONS: Given the variable appearance of the local recurrence after breast conservation therapy, any suspicious finding needs to be carefully evaluated regardless of the mammographic appearance of the original tumor.

Biopsy findings after breast conservation therapy for early-stage invasive breast cancer.

PURPOSE: To determine the patterns and factors predictive of positive ipsilateral breast biopsy after conservation therapy for early-stage breast cancer. METHODS AND MATERIALS: We performed a retrospective review of Stage I-II breast cancer patients initially treated with lumpectomy and radiotherapy between 1977 and 1996, who later underwent post-treatment ipsilateral breast biopsies. RESULTS: A total of 223 biopsies were performed in 193 treated breasts: 171 single and 22 multiple biopsies. Of the 223 biopsies, 56% were positive and 44% were negative for recurrence. The positive biopsy rate (PBR) was 59% for the first and 32% for subsequent biopsies. The median time to the first post-treatment biopsy was 49 months. Of the patients with negative initial biopsy findings, 11% later developed local recurrence. The PBR was 40% among patients with physical examination findings only, 65% with mammographic abnormalities only, and 79% with both findings (p = 0.001). Analysis of the procedure type revealed a PBR of 86% for core and 58% for excisional biopsies compared with 28% for aspiration cytology alone (p = 0.025). The PBR varied inversely with age at the original diagnosis: 49% if >or=51 years, 57% if 36-50 years, and 83% if 180 months after completing postlumpectomy radiotherapy (p = 0.01). The PBR was not linked with recurrence location, initial pathologic T or N stage, estrogen receptor/progesterone receptor status, or final pathologic margins (all p >or= 0.15). CONCLUSION: After definitive radiotherapy for early-stage breast cancer, a greater PBR was associated with the presence of both mammographic and clinical abnormalities, excisional or core biopsies, younger age at the initial diagnosis, and longer intervals after radiotherapy completion.

Time to Surgery and Breast Cancer Survival in the United States.

IMPORTANCE: Time to surgery (TTS) is of concern to patients and clinicians, but controversy surrounds its effect on breast cancer survival. There remains little national data evaluating the association. OBJECTIVE: To investigate the relationship between the time from diagnosis to breast cancer surgery and survival, using separate analyses of 2 of the largest cancer databases in the United States. DESIGN, SETTING, AND PARTICIPANTS: Two independent population-based studies were conducted of prospectively collected national data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database and the National Cancer Database (NCDB). The SEER-Medicare cohort included Medicare patients older than 65 years, and the NCDB cohort included patients cared for at Commission on Cancer-accredited facilities throughout the United States. Each analysis assessed overall survival as a function of time between diagnosis and surgery by evaluating 5 intervals (≤30, 31-60, 61-90, 91-120, and 121-180 days) and disease-specific survival at 60-day intervals. All patients were diagnosed with noninflammatory, nonmetastatic, invasive breast cancer and underwent surgery as initial treatment. MAIN OUTCOMES AND MEASURES: Overall and disease-specific survival as a function of time between diagnosis and surgery, after adjusting for patient, demographic, and tumor-related factors. RESULTS: The SEER-Medicare cohort had 94 544 patients 66 years or older diagnosed between 1992 and 2009. With each interval of delay increase, overall survival was lower overall (hazard ratio [HR], 1.09; 95% CI, 1.06-1.13; P < .001), and in patients with stage I (HR, 1.13; 95% CI, 1.08-1.18; P < .001) and stage II disease (HR 1.06; 95% CI, 1.01-1.11; P = .01). Breast cancer-specific mortality increased with each 60-day interval (subdistribution hazard ratio [sHR], 1.26; 95% CI, 1.02-1.54; P = .03). The NCDB study evaluated 115 790 patients 18 years or older diagnosed between 2003 and 2005. The overall mortality HR was 1.10 (95% CI, 1.07-1.13; P < .001) for each increasing interval, significant in stages I (HR, 1.16; 95% CI, 1.12-1.21; P < .001) and II (HR, 1.09; 95% CI, 1.05-1.13; P < .001) only, after adjusting for demographic, tumor, and treatment factors. CONCLUSIONS AND RELEVANCE: Greater TTS is associated with lower overall and disease-specific survival, and a shortened delay is associated with benefits comparable to some standard therapies. Although time is required for preoperative evaluation and consideration of options such as reconstruction, efforts to reduce TTS should be pursued when possible to enhance survival.

The association of cytokeratin-only-positive sentinel lymph nodes and subsequent metastases in breast cancer.

INTRODUCTION: The purpose of this study was to better characterize the clinical significance of cytokeratin immunohistochemistry (IHC)-only-positive lymph node metastases among patients with breast cancer. METHODS: We performed a retrospective review of 334 patients who underwent sentinel lymph node (SLN) biopsy from 1 February 1997 through 31 July 2001. SLN biopsies were evaluated using standard hematoxylin and eosin (H&E) techniques. If H&E was negative, cytokeratin IHC was performed. We then evaluated the incidence of subsequent regional and distant metastatic disease. RESULTS: Cytokeratin IHC was performed on 183 sentinel node biopsies from 180 patients comprising a total of 427 sentinel lymph nodes. The procedures included lumpectomy and SLN biopsy (n = 83), mastectomy with SLN biopsy (n = 7), lumpectomy with SLN biopsy and completion axillary dissection (n = 80), and modified radical mastectomy with SLN biopsy and completion axillary dissection (n = 13). Cytokeratin IHC was negative in 175 axillary specimens and positive in 8 (4.4%) from 8 different patients. In these eight specimens, deeper sections with subsequent H&E staining additionally identified micrometastasis in four patients. Three of these 8 patients (37.5%) developed distant metastatic disease compared with 1 of the 172 patients (0.6%) with negative cytokeratin IHC (P < .001). Additionally, one of the cytokeratin-positive patients developed regional nodal metastasis compared with none of the 172 cytokeratin-negative patients. CONCLUSIONS: Cytokeratin IHC provides a clinically relevant adjunct to H&E staining for evaluating sentinel lymph nodes in breast cancer. These data suggest that patients with cytokeratin-positive sentinel nodes are at increased risk for development of regional and distant metastatic disease.

Invasive mucinous carcinoma arising in ectopic axillary breast tissue: a case report and literature review.

BACKGROUND: Invasive mucinous carcinoma arising in ectopic axillary breast tissue is an uncommon diagnosis. While some published medical literature makes recommendations regarding the management of ectopic primaries, many of these recommendations are outdated. We therefore hope to provide general guidance with the management of this rare entity. CASE REPORT: We report a case of a 70-year-old woman with primary invasive mucinous carcinoma of ectopic breast tissue. A literature study was performed on primary ectopic breast carcinoma. This case report with review of the literature was performed to provide rationales for a more conservative treatment based upon current data and treatment paradigms. Although the diagnosis of primary ectopic breast carcinoma is uncommon, the presence of a suspicious nodule along the mammary ridge should alert the clinician to consider the possibility of this diagnosis. A mammogram and ultrasound of the nodule were performed and the suspicious nodule was biopsied, confirming the diagnosis. Breast conservation was performed with standard nodal evaluation. CONCLUSIONS: The management of primary ectopic breast carcinoma should be based upon current breast conservation techniques of orthotopic breast cancer. Current data suggest that standard treatment paradigms remain applicable to this rare clinical entity.

Skin involvement and breast cancer: are T4b lesions of all sizes created equal?

BACKGROUND: Nonmetastatic, noninflammatory, invasive breast cancers with skin involvement (SI) are classified as T4b, regardless of size. This study evaluated disease-specific survival (DSS) to determine whether size should be considered for these lesions rather than grouping them all into stage III. STUDY DESIGN: Surveillance, Epidemiology, and End Results data linked to Medicare claims were reviewed. Skin involved and non-SI tumors were reclassified using the American Joint Committee on Cancer, 7(th) edition groupings using tumor size and nodal involvement alone without considering SI (neostage). Disease-specific survival was adjusted for demographics, histology, and treatment using competing risk methods with propensity score-based weighting and bootstrap standard errors. RESULTS: Among 924 SI patients diagnosed between 1992 and 2005, tumors were 0.1 to 2.0 cm, 2.1 to 5.0 cm, and >5.0 cm in 11.6%, 51.1%, and 37.3% of patients, respectively. There were no nodal metastases in 22.3%, 1 to 3 positive nodes in 31.7%, 4 to 9 positive in 28.6%, and ≥10 positive in 17.4% of patients. For SI patients, adjusted 5-year DSS was 95.8% (95% CI, 95.6-96.0) for neostage I, declining progressively to 36.4% (95% CI, 33.8-39.2) for neostage IIIC patients. Adjusted 5-year DSS for SI and non-SI tumors (n = 66,185) was similar for neostage I, IIA, and IIB, and markedly lower for IIIA and IIIC. Adjusted DSS for SI IIIA was similar to non-SI IIIC. CONCLUSIONS: Noninflammatory SI breast cancers have widely varied DSS that differs by tumor size and nodal involvement and therefore should not all be stage III. Skin involvement should be subordinate to T and N groupings to classify SI with non-SI lesions having similar prognoses.

Preoperative delays in the US Medicare population with breast cancer.

PURPOSE: Although no specific delay threshold after diagnosis of breast cancer has been demonstrated to affect outcome, delays can cause anxiety, and surgical waiting time has been suggested as a quality measure. This study was performed to determine the interval from presentation to surgery in Medicare patients with nonmetastatic invasive breast cancer who did not receive neoadjuvant chemotherapy and factors associated with a longer time to surgery. METHODS: Medicare claims linked to Surveillance, Epidemiology, and End Results data were reviewed for factors associated with delay between the first physician claim for a breast problem and first therapeutic surgery. RESULTS: Between 1992 and 2005, 72,586 Medicare patients with breast cancer had a median interval (delay) between first physician visit and surgery of 29 days, increasing from 21 days in 1992 to 32 days in 2005. Women (29 days v 24 days for men; P < .001), younger patients (29 days; P < .001), blacks and Hispanics (each 37 days; P < .001), patients in the northeast (33 days; P < .001), and patients in large metropolitan areas (32 days; P < .001) had longer delays. Patients having breast conservation and mastectomies had adjusted median delays of 28 and 30 days, respectively, with simultaneous reconstruction adding 12 days. Preoperative components, including imaging modalities, biopsy type, and clinician visits, were also each associated with a specific additional delay. CONCLUSION: Waiting times for breast cancer surgery have increased in Medicare patients, and measurable delays are associated with demographics and preoperative evaluation components. If such increases continue, periodic assessment may be required to rule out detrimental effects on outcomes.