Predictors of locoregional recurrence among patients with early-stage breast cancer treated with breast-conserving therapy

Background Our aim was to identify predictors of locoregional recurrence (LRR) in patients with early-stage breast cancer treated with breast-conserving therapy (BCT) and long-term follow-up. Methods From 1970 to 1994, 1153 patients with stage I to II breast cancer underwent BCT and radiotherapy at our institution. Patients with prior breast cancer or other primary malignancies were excluded. Clinical and pathologic characteristics evaluated were age, race, tumor size, stage, pathologic tumor margins, axillary nodal involvement, estrogen and progesterone receptor status, Black's nuclear grade, type of surgery, and use of adjuvant therapy. Results Of 1083 patients, 54% presented with stage I disease and 46% with stage II disease. Median age was 50 years, and median follow-up was 9 years. Axillary nodes were positive in 31% of the patients who underwent axillary dissection. LRR developed in 6%, LRR followed by systemic recurrence in 5%, and systemic recurrence alone in 13%, 76% had no evidence of recurrence at last follow-up. Age, tumor size, positive lymph nodes, and not receiving chemotherapy or hormonal therapy were independent predictors of LRR. Disease-specific survival among patients with LRR was similar to that among patients with no recurrence. Conclusions Multidisciplinary treatment strategies should be used to accomplish durable locoregional control after BCT. Presented at the 54th Annual Cancer Symposium of the Society of Surgical Oncology, Washington, DC, March 15–18, 2001.     

Long-term complications associated with breast-conservation surgery and radiotherapy

Background Breast-conservation surgery plus radiotherapy has become the standard of care for early-stage breast cancer; we evaluated its long-term complications. Methods We selected patients treated with surgery and radiotherapy between January 1990 and December 1992 (an era in which standard radiation dosages were used) with follow-up for at least 1 year. Patients were prospectively monitored for treatment-related complications. Median follow-up time was 89 months. Results A total of 294 patients met the selection criteria. Grade 2 or higher late complications were identified in 29 patients and included arm edema in 13 patients, breast skin fibrosis in 12, decreased range of motion in 4, pneumonitis in 2, neuropathy in 2, fat necrosis in 1, and rib fracture in 1. Arm edema was more common after lumpectomy plus axillary node dissection than after lumpectomy alone. Arm edema occurred in 18% of patients who underwent surgery plus irradiation of the lymph nodes and 10% who underwent surgery without nodal irradiation. Conclusions Breast-conservation surgery plus radiotherapy was associated with grade 2 or higher complications in only 9.9% of patients. Half of these complications were attributable to axillary dissection, it is hoped that lower complication rates can be achieved with sentinel lymph node biopsy.     

Prognostic Implications of Pathological Lymph Node Status After Preoperative Chemotherapy for Operable T3N0M0 Breast Cancer

Background: Although preoperative chemotherapy has become the standard of care for inoperable locally advanced breast cancer, its role for downstaging resectable primary tumors is still evolving. The purpose of this study was to determine whether the prognostic information from an axillary node dissection in patients with clinical T3N0 breast cancer was altered by preoperative chemotherapy compared with surgery de novo.Methods: Between 1976 and 1994, 91 patients with clinically node-negative operable T3 breast cancer received doxorubicin-based combination chemotherapy on protocol at one institution. Fifty-three patients received both preoperative and postoperative chemotherapy (PreopCT), and 38 received postoperative chemotherapy only (PostopCT). All patients underwent axillary lymph node dissection as part of their definitive surgical treatment. There were no differences between the PreopCT and PostopCT groups in median age (51 vs. 49 years), median tumor size at presentation (6 cm vs. 6 cm), tumor grade, or estrogen receptor status (estrogen receptor negative 38% vs. 32%). The median follow-up time was 7 years.Results: Patients in the PreopCT group had fewer histologically positive lymph nodes (median, 0 vs. 3, P < .01), and a lower incidence of extranodal extension (19% vs. 42%, P 5 .02). By univariate analysis, the number of pathologically positive lymph nodes (P < .01) and extranodal extension (P < .01) were predictors of disease-specific survival in PreopCT patients. Multivariate analysis showed that extranodal extension was the only independent prognostic factor in PreopCT patients (P < .01). Overall, PreopCT and PostopCT patients had similar 5-year disease-free survival rates (66% vs. 57%); however, PreopCT patients had worse disease-free (P 5 .01) and diseasespecific survival (P 5 .04) when survival was compared after adjustment for the number of positive lymph nodes. Furthermore, PreopCT patients with 4–9 positive lymph nodes had a lower 5-year disease-free survival rate than PostopCT patients with 4–9 positive nodes (17 vs. 48%, P 5 .04).Conclusions: Axillary lymph node status remains prognostic after chemotherapy. Pathologically positive lymph nodes after preoperative chemotherapy are associated with a worse prognosis than the same nodal status before chemotherapy.     

Surgery After Downstaging of Unresectable Hepatic Tumors With Intra-Arterial Chemotherapy

Background: This retrospective study was performed to assess the outcome among patients who underwent hepatic resection or tumor ablation after hepatic artery infusion (HAI) therapy downstaged previously unresectable hepatocellular carcinoma (HCC) or liver metastases from colorectal cancer (CRC).Methods: Between 1983 and 1998, 25 patients with HCC and 383 patients with hepatic CRC metastases were treated with HAI therapy for unresectable liver disease. We retrospectively reviewed the records of 26 (6%) of these patients who underwent subsequent surgical exploration for tumor resection or ablation.Results: At a median of 9 months (range 7–12 months) after HAI treatment, four patients (16%) with HCC underwent exploratory surgery; two underwent resection with negative margins, and the other two were given radiofrequency ablation (RFA) because of underlying cirrhosis. At a median postoperative follow-up of 16 months (range 6–48 months), all four patients were alive with no evidence of disease. At a median of 14.5 months (range 8–24 months) after HAI therapy, 22 patients with hepatic CRC metastases underwent exploratory surgery; 10 underwent resection, 6 underwent resection and RFA or cryotherapy, and 2 underwent RFA only. At a median follow-up of 17 months, 15 (83%) of the 18 patients with CRC who had received surgical treatment had developed recurrent disease; the other 3 died of other causes (1 of postoperative complications) within 7 months of the surgery. One patient in whom disease recurred underwent a second resection and was disease-free at 1 year follow-up.Conclusions: Hepatic resection or ablation after tumor downstaging with HAI therapy is a viable option for patients with unresectable HCC. However, given the high rate of recurrence of metastases from CRC, hepatic resection or ablation after downstaging with HAI should be used with caution.Presented at the 53rd Annual Meeting of the Society of Surgical Oncology, New Orleans, Louisiana, March 16–19, 2000.     

Does tonsillectomy reduce the risk of being a habitual or severe snorer?

We assessed the relationship between tonsillectomy and being a habitual or severe snorer. Volunteers were asked to provide their age and sex, a detailed snoring history covering the frequency and intensity of snoring, and their smoking and alcohol intake habits. After oral and nasal examinations, the tonsil size scores, Mallampati index scores, and nasal obstructions of the volunteers were recorded. Body heights and weights were measured, and body mass indexes were calculated. Being male, aging, an increase in body mass index and tonsillectomy were identified as independent risk factors for being a habitual and severe snorer. Although a nasal obstruction was found to be an independent risk factor for being a habitual snorer, an obstructive tongue base was identified as an independent risk factor for being a severe snorer. Tonsillectomy reduces the risk of being both a habitual and severe snorer. This reduced incidence and intensity of snoring following tonsillectomy could be accepted as a long-term beneficial side effect of the operation.     

Clinical outcome of patients with lymph node-negative breast carcinoma who have sentinel lymph node micrometastases detected by immunohistochemistry

BACKGROUND: The ideal pathologic assessment of sentinel lymph nodes (SLNs) in patients with breast carcinoma remains controversial. The authors evaluated how detailed assessment of SLNs using immunohistochemistry (IHC) and serial sectioning would affect treatment decisions and outcomes in patients with breast carcinoma who had negative SLNs on standard hematoxylin and eosin staining. METHODS: The SLNs from patients who were treated between June 1998 and June, 1999 and who had negative lymph node status determined by hematoxylin and eosin staining (n = 84 patients) were evaluated further with serial sectioning and cytokeratin IHC. Patients were offered adjuvant therapy based on primary tumor factors. RESULTS: The median patient age was 57 years, and the median tumor size was 1.2 cm. At a median follow-up of 40.2 months, 81 patients (96%) were alive with no evidence of disease, 1 patient was alive with disease, 1 patient had died of disease, and 1 patient had died of other causes. Fifteen patients (18%) had micrometastases identified on IHC. Of the total 84 patients, information regarding adjuvant therapy was not available for 5 patients. Of the remaining 79 patients, 10 patients (13%) were not offered adjuvant chemotherapy but had positive SLN status determined by IHC. SLN status based on IHC evaluation did not correlate with age (P = 0.077), tumor size (P = 0.717), grade (P = 0.148), estrogen receptor status (P = 1.000), or lymphovascular invasion (P = 0.274). Furthermore, IHC-detected positive SLN status did not correlate with distant metastasis (P = 0.372) or overall or distant metastasis-free survival (P = 0.543 and P = 0.540, respectively). CONCLUSIONS: Although the finding of SLN micrometastases by IHC may change management in > 12% of patients, preliminary results suggested that such micrometastases do not affect outcomes significantly.     

Predictors of systemic recurrence and disease-specific survival after ipsilateral breast tumor recurrence

BACKGROUND: In patients with breast carcinoma, ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) is an independent predictor of systemic recurrence and disease-specific survival (DSS). However, only a subgroup of patients with IBTR develop systemic recurrences. Therefore, the management of isolated IBTR remains controversial. The objective of the current study was to identify determinants of systemic recurrence and DSS after IBTR. METHODS: The medical records of 120 women who underwent BCT for Stage 0-III breast carcinoma between 1971 and 1996 and who subsequently developed isolated IBTR were reviewed. Clinicopathologic factors were studied using univariate and multivariate analyses for their association with DSS and the development of systemic recurrence after IBTR. RESULTS: The median time to IBTR was 59 months. At a median follow-up of 80 months after IBTR, 45 patients (37.5%) had a systemic recurrence. Initial lymph node status was the strongest predictor of systemic recurrence according to the a univariate analysis (P = 0.001). Other significant factors included lymphovascular invasion (LVI) in the primary tumor, time to IBTR < or = 48 months, clinical and pathologic IBTR tumor size > 1 cm, LVI in the recurrent tumor, and skin involvement at IBTR. In a multivariate logistic regression analysis, initially positive lymph node status (relative risk [RR], 5.3; 95% confidence interval [95% CI], 1.4-20.1; P = 0.015) and skin involvement at IBTR (RR, 15.1; 95% CI, 1.5-153.8; P = 0.022) remained independent predictors of systemic recurrence. The 5-year and 10-year DSS rates after IBTR were 78% and 68%, respectively. In a multivariate Cox proportional hazards model analysis, only LVI in the recurrent tumor was found to be an independent predictor of DSS (RR, 4.6; 95% CI, 1.5-14.1; P = 0.008). CONCLUSIONS: Patients who initially had lymph node-positive disease or skin involvement or LVI at IBTR represented especially high-risk groups that warranted consideration for aggressive, systemic treatment and novel, targeted therapies after IBTR. Determinants of prognosis after IBTR should be taken into account when evaluating the need for further systemic therapy and designing risk-stratified clinical trials.     

Improving local control with breast-conserving therapy: a 27-year single-institution experience

BACKGROUND: The risk of ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) is associated with treatment and tumor-related variables, such as surgical margin status and the use of systemic therapy, and these variables have changed over time. Correspondingly, the authors of the current study hypothesized that the contemporary multidisciplinary management of breast carcinoma would lead to an improvement in IBTR rates after BCT. METHODS: Between 1970 and 1996, 1355 patients with pathologic Stage I-II invasive breast carcinoma underwent BCT (breast-conserving surgery and adjuvant radiation therapy) at The University of Texas M. D. Anderson Cancer Center. Contemporary methods of analyzing surgical margins were in routine use by 1994. To analyze the effect of this variable and others, patient and tumor characteristics and IBTR rates in patients treated during 1994-1996 were compared with those in patients treated from 1970 to 1993. RESULTS: Characteristics were similar in patients treated during 1994-1996 (n = 381) and those treated before 1994 (n = 974) except for patients aged >50 years (63.3% vs. 51.7%, P < 0.001), and patients who had a family history of breast carcinoma (37.9% vs. 30.8%, P = 0.017). Patients treated after 1994 were less likely to have positive or unknown margins (2.9 % vs. 24.1 %, P = 0.0001), more likely to receive chemotherapy (40.5% vs. 26%, P < 0.001), and more likely to receive hormonal therapy (33.3% vs. 19.4%, P < 0.001), but less likely to receive radiation boosts to the primary tumor bed (59.8% vs. 89%, P < 0.001). The 5-year cumulative IBTR rate was significantly lower among patients treated in 1994-1996 than among patients treated before 1994 (1.3% vs. 5.7%, P = 0.001) largely because of the drop in IBTR rates among patients aged < or = 50 years (1.4 % vs. 9.1 %, P = 0.0001). On multivariate analysis, age > 50 (hazards ratio [HR] = 0.401; P = 0.0001), presence of negative surgical margins (HR = 0.574; P = 0.017), and use of adjuvant hormonal therapy (HR = 0.402; P = 0.05) were independent predictors of improved 5-year IBTR-free survival. On subgroup analysis, use of chemotherapy was associated with increased IBTR-free survival among women aged < or = 50 years (HR = 0.383; P = 0.001). Although 5-year cumulative IBTR rates were lower among women aged > 50 years than among younger women before 1994 (2.6 % vs. 9.1%, P < 0.0001), no such difference was found in the group treated in 1994-1996 (1.2 % for age > 50 yrs vs. 1.4 % for < or = 50 yrs, P = 0.999). CONCLUSIONS: The IBTR rate after BCT appears to be declining, especially among patients < 50 years of age. However, long-term follow-up is necessary to confirm this finding. This finding may reflect changes in surgical approaches and pathologic evaluation as well as an increased use of systemic therapy. The current low incidence of IBTR with multidisciplinary management of breast carcinoma may result in more patients choosing BCT over mastectomy.