Compliance with consensus recommendations for the treatment of early stage breast carcinoma in elderly women

BACKGROUND: The goal of this study was to assess variations with age in the management of breast carcinoma and to identify determinants of care received. METHODS: A stratified random sample was selected among women age > or = 50 newly diagnosed with lymph node negative breast carcinoma in Quebec in 1988, 1991, and 1993. Information was abstracted from medical charts. Predictors of definitive locoregional treatment (total mastectomy with lymph node dissection or breast-conserving surgery with both axillary lymph node dissection and radiation therapy) were identified by multiple logistic regression analysis. RESULTS: Overall, 1174 patients age > or = 50 years with breast carcinoma were included. Women age > or = 70 years were much less likely to receive definitive locoregional treatment compared with women ages 50-69 years (48.7% vs. 83.5%; P < 0.0001). Older women were less likely to undergo surgery with breast preservation (76.7% vs. 86.3%; P < 0.0001), radiation therapy (54.7% vs. 90.5%; P < 0.0001), dissection of the axillary lymph nodes (55.6% vs. 86.3%; P < 0.0001), or chemotherapy (1.2% vs. 13.9%; P < 0.0001), but not treatment with tamoxifen (66.4% vs. 64.7%; P = 0.41). Adjusting for comorbidity and other characteristics related to the disease, the hospital, and the attending physician, age remained a strong determinant of the probability of receiving definitive locoregional treatment (odds ratio [OR], 0.14; 95% confidence interval [95% CI], 0.12-0.18 for women age > or = 70 years vs. women ages 50-69 years). The same association was observed when women who did not undergo lymph node dissection but who received systemic adjuvant treatment were considered to have received definitive therapy (OR, 0.13; 95% CI, 0.10-0.17) for women age > or = 70 years vs. women ages 50-69 years). CONCLUSIONS: Less aggressive patterns of care are provided to elderly breast carcinoma patients, independent of comorbidity. This could explain, at least in part, the sustained breast carcinoma mortality in this population.     

Pre-diagnostic NSAID use but not hormone therapy is associated with improved colorectal cancer survival in women

Background:

Non-steroidal anti-inflammatory drugs (NSAIDs) and hormone therapy (HT) independently decrease the risk of colorectal cancer. However, their role in altering survival after a colorectal cancer diagnosis is not well established.

Methods:

We examined the association between the use of these common medications before diagnosis and colorectal cancer survival among women in western Washington State diagnosed with incident colorectal cancer from 1997 to 2002. Cases were ascertained using the Surveillance, Epidemiology and End Results cancer registry; mortality follow-up was completed through linkages to the National Death Index. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results:

We observed no overall association between colorectal cancer survival and pre-diagnostic NSAID use. However, when stratified by tumour sub-site, NSAID use was associated with a reduced risk of colorectal cancer mortality for women diagnosed with proximal (HR=0.55; 95% CI: 0.32–0.92), but not distal or rectal (HR=1.32; 95% CI: 0.83–2.10) tumours. The usage of HT was not associated with colorectal cancer survival overall or by tumour sub-site.

Conclusion:

Usage of NSAIDs before diagnosis may be associated with improved colorectal cancer survival among women diagnosed with proximal tumours. The usage of HT does not appear to have a function in altering colorectal cancer mortality.     

CD44 expression is associated with increased survival in node-negative invasive breast carcinoma.

PURPOSE: CD44 is a multifunctional cell surface receptor with many known splice variants, some of which have been reported to play a role in tumor progression. The purpose of this study was to evaluate the prognostic significance of CD44 isoforms in early-stage, lymph node-negative invasive breast carcinoma. EXPERIMENTAL DESIGN: Immunohistochemical staining for CD44 isoforms was done on archival paraffin tissue sections of invasive breast carcinoma from a cohort of lymph node-negative patients who received no adjuvant tamoxifen or chemotherapy and who had a mean clinical follow-up period of 15 years. Immunohistochemical staining was done with antibodies to CD44s, the standard isoform of CD44, and to isoforms containing variant exon 6 (CD44v6); levels of staining were correlated with clinical outcome data. RESULTS: There was a trend towards increased disease-free survival for patients whose tumors had high anti-CD44s positivity (P = 0.05), and a significant association was observed between anti-CD44s positivity and disease-related survival (P = 0.04). Expression of CD44v6 isoforms did not correlate with clinical outcome. CONCLUSION: CD44 expression, as assessed by immunohistochemical staining with anti-CD44s, may be a favorable prognostic factor in patients with node-negative invasive breast carcinoma.     

New prognostic factors associated with long-term survival in node-negative breast cancer patients

Background  This study was undertaken to determine the absolute and relative value of angiogenesis, proliferating cell nuclear antigen (PCNA) and conventional prognostic factors in predicting relapse-free survival (RFS) and overall survival (OS) rates associated with long-term survival in Japanese patients with node-negative breast cancer. Patients and Methods  Two hundred patients with histological node-negative breast cancer were studied. We investigated nine clinicopathological factors, including angiogenesis, PCNA using permanent-section immunohistochemistry, clinical tumor size, histological grade (HG), tumor necrosis, lymphatic vessel invasion (LVI), histological extension, histological classification, and infiltrating growth (INF), followed for a median of 10 years (range, 1 to 20). Results  Twenty-one patients (10.5%) had recurrence and 15 patients (7.5%) died of breast cancer. Univariate analysis showed that PCNA, clinical tumor size, HG, angiogenesis, and LVI were significantly predictive of 20-year RFS or OS. Tumor necrosis was significantly predictive of OS, not of RFS. Multivariate analysis showed that clinical tumor size (P=0.0003), angiogenesis (P=0.0003), PCNA (P= 0.0064), and HG (P=0.0401) were significant independent prognostic factors for RFS. PCNA (P< 0.0001) and clinical tumor size (P=0.0112) were significant independent prognostic factors for OS, while angiogenesis was a borderline significant factor. Conclusion  PCNA and angiogenesis were important new prognostic factors in node-negative breast cancer patients.     

Elevated T cell activation score is associated with improved survival of breast cancer

Purpose

Immune checkpoints cytotoxic T lymphocyte antigen 4 (CTLA4) and programmed cell death 1 receptor (PD-1) negatively regulate CD8⁺ T cell functions, impeding the capacity of effector T cells to kill tumors. Here, we study the prognostic significance of CTLA4, PD-1 and T cell activation status in breast cancer.

Methods

Using a publicly accessed RNA-seq dataset including 1087 breast cancer patients, we performed Kaplan–Meier survival curves and multivariate Cox regression models to evaluate the associations of CTLA4, PD-1, and weighted T cell activation score with patients’ overall survival.

Results

Survival analyses showed that high CTLA4 but low PD-1 expression was associated with a poor overall survival, and that high T cell activation score was associated with an improved survival. The median survival was 216.6 months (95% CI 114.1–244.9) for the T activation group, 127.0 months (95% CI 112.3–212.1) for the intermediate, and 120.5 months (95% CI 93.8 to ∞) for the exhaustion (Log-rank p = 0.084). This association was verified in multivariate Cox regression analysis. The hazard ratios were 0.81 (95% CI 0.56–1.19) for the intermediate group, and 0.48 (95% CI 0.26–0.86) for the activation group, respectively, in comparison to the exhaustion group (p value for trend = 0.016).

Conclusions

T cell activation score has significantly positive relationship with patients’ overall survival, and may serve as a marker of personalized immunotherapy in breast cancer patients. Cocktail rather than single immune checkpoint blockade may yield more benefit for breast cancer patients.

     

Clinicopathologic study associated with long-term survival in Japanese patients with node-negative breast cancer

This study was undertaken to determine the absolute and relative value of blood vessel invasion (BVI) using both factor VIII-related antigen and elastica van Gieson staining, proliferating cell nuclear antigen (PCNA), p53, c-erbB-2, and conventional prognostic factors in predicting relapse-free survival (RFS) and overall survival (OS) rates associated with long-term survival in Japanese patients with node-negative breast cancer. Two hundred patients with histological node-negative breast cancer were studied. We investigated nine clinicopathological factors, including PCNA, p53, c-erbB-2 using permanent-section immunohistochemistry, clinical tumour size (T), histological grade (HG), mitotic index (MI), tumour necrosis (TN), lymphatic vessel invasion (LVI) and BVI, followed for a median of 10 years (range 1-20). Twenty-one patients (10.5%) had recurrence and 15 patients (7.5%) died of breast cancer. Univariate analysis showed that BVI, PCNA, T, HG, MI, p53, c-erbB-2 and LVI were significantly predictive of 20-year RFS or OS. Multivariate analysis showed that BVI (P = 0.0159, P = 0.0368), proliferating cell nuclear antigen (PCNA) (P = 0.0165, P = 0.0001), and T (P = 0.0190, P = 0.0399) were significantly independent prognostic factors for RFS or OS respectively. BVI, PCNA and T were independent prognostic indicators for RFS or OS in Japanese patients with node-negative breast cancer and are useful in selecting high-risk patients who may be eligible to receive strong adjuvant therapies.     

Definitive local therapy is associated with improved overall survival in metastatic cervical cancer

Purpose

Definitive local therapy is often used in metastatic cervical cancer to reduce morbidity associated with local tumor progression. However, the potential benefit of this therapeutic approach has not been rigorously investigated. We hypothesized that definitive local therapy is associated with improved overall survival (OS) in metastatic cervical cancer.

Good clinical response of breast cancers to neoadjuvant chemoendocrine therapy is associated with improved overall survival.

BACKGROUND: We present extended follow-up from a prospective randomised trial evaluating the role of neoadjuvant chemoendocrine therapy in the treatment of operable breast cancer. PATIENTS AND METHODS: 309 women were randomised to primary surgery followed by eight cycles of adjuvant mitoxantrone, methotrexate with tamoxifen (2MT) or 2MT with mitomycin-C (3MT) versus the same regimen for four cycles before followed by four cycles after surgery. For this analysis the median follow-up of patients was 112 months. RESULTS: After 10 years follow-up there is still no statistically significant difference in disease-free survival (DFS) (71% versus 71%) or overall survival (OS) (63% versus 70%) when comparing adjuvant versus neoadjuvant treatment, respectively. Of 144 evaluable patients in the neoadjuvant arm, 74 achieved a good clinical response and 70 patients achieved a poor clinical response. Good responders had a superior DFS (80% versus 64%, P=0.01) and OS (77% versus 63%, P=0.03) compared to poor responders. CONCLUSIONS: At 10 years, neoadjuvant and adjuvant treatment continue to have equivalent OS and DFS. Good clinical response to neoadjuvant chemotherapy is associated with superior DFS and OS. This supports the use of clinical response of primary breast cancer to neoadjuvant therapy as a surrogate marker of survival benefit.     

Time trends in systemic adjuvant treatment for node-negative breast cancer.

PURPOSE: We conducted a population-based study in Quebec, Canada, to assess longitudinal changes in systemic adjuvant therapy for node-negative breast cancer. MATERIALS AND METHODS: A stratified random sample was selected among women with newly diagnosed node-negative breast cancer in 1988, 1991, and 1993. Information on the patient, her tumor, source of care, and treatment was abstracted from medical charts. Patients were classified as being at minimal, moderate, or high risk of recurrence on the basis of criteria proposed at the 4th International Conference on Adjuvant Therapy of Primary Breast Cancer (St. Gallen, Switzerland, 1992), and systemic adjuvant treatment received was dichotomized as being consistent or not consistent with consensus recommendations. RESULTS: Overall, 1,578 cases of invasive breast carcinoma were reviewed. The proportion of patients who were given hormonal or cytotoxic treatment increased from 51.7% to 73.1% from 1988 to 1993. Virtually all women at minimal risk were treated in 1991 and 1993 according to the consensus statement. The proportions of women so treated were 75.0% and 65.4% in the moderate- and high-risk categories, respectively, in 1991. In 1993, these proportions were 71.4% and 67.0%, respectively. Omission of chemotherapy, especially in high-risk women with estrogen receptor-negative tumors who were 50 to 69 years of age, was the most frequent inconsistency with guidelines. CONCLUSION: Systemic adjuvant therapy for node-negative breast cancer has gained acceptance. Better understanding of the decision-making process, of the perception of the risks and benefits involved, and of the impact of alternative strategies for the dissemination of consensus recommendations are needed to promote the use of chemotherapy in specific categories of women who are at high risk of recurrence.     

Impact of systemic treatment on local control for patients with lymph node-negative breast cancer treated with breast-conservation therapy.

PURPOSE: To determine the impact of tamoxifen and chemotherapy on local control for breast cancer patients treated with breast-conservation therapy. PATIENTS AND METHODS: The data from 484 breast cancer patients who were treated with breast-conserving surgery and radiation were analyzed. Only patients with lymph node-negative disease were studied to provide comparative groups with a similar stage of disease and a similar competing risk for distant metastases. Actuarial local control rates of the 277 patients treated with systemic therapy (128, chemotherapy with or without tamoxifen; 149, tamoxifen alone) were compared with the rates for the 207 patients who received no systemic treatment. Only 10% of the patients had positive (2%), close (3%), or unknown margin status (5%). RESULTS: Patients treated with systemic therapy had improved 5-year (97.5% v 89.8%) and 8-year (95.6% v 85.2%) local control rates compared with those that did not receive systemic treatment (P =.004, log-rank test). There was no statistical difference in local control between patients treated with chemotherapy and patients treated with tamoxifen alone (P =.219). Systemic treatment, margin status, young patient age, estrogen and progesterone receptor status, and primary tumor size were analyzed in a Cox regression analysis. The use of systemic treatment was the most powerful predictor of local control: patients who did not receive systemic treatment had a relative risk of local recurrence of 3.3 (95% confidence interval, 1.5 to 7.5; P =.004). CONCLUSION: In this retrospective analysis, systemic therapy appears to contribute to long-term local control in patients with lymph node-negative breast cancer treated with breast-conservation therapy.     

Surgery in combination with systemic chemotherapy is associated with improved survival in stage IV gallbladder cancer

BackgroundGallbladder cancer (GBC) is the most common biliary malignancy frequently metastatic at diagnosis with poor prognosis. While surgery remains the standard for early-stage GBC, the role of surgery in patients with metastatic gastrointestinal cancers is expanding due to improvements in systemic therapies. We sought to evaluate the survival of patients with stage IV GBC undergoing surgery in an era of improved multi-agent systemic therapy.MethodsA retrospective review of the National Cancer Database was performed. Patients with stage IV GBC who underwent systemic therapy were included. Patients who received radiation therapy, palliative therapy or had missing survival data were excluded. Univariable and multivariable analysis was performed.Results4,145 patients were identified between 2004 and 2016. Mean age was 69. Surgery combined with systemic therapy predicted improved median survival compared with chemotherapy alone (11.1mo versus 6.8mo, HR 0.65, p < 0.001). Additionally, receipt of treatment after 2011 predicted improved survival (HR 0.86, p < 0.001). Patients treated with multi-agent chemotherapy in combination with surgery were associated with the greatest hazard ratio benefit (0.40, p < 0.001) versus single agent therapy alone.ConclusionPatients with stage IV gallbladder cancer treated with a combination of surgery and chemotherapy are associated with an improved overall survival compared to chemotherapy alone. Patients receiving care during the more recent era demonstrated improved survival. These results support a role for surgery in selected patients with stage IV gallbladder cancer receiving chemotherapy.     

Validation and problems of St-Gallen recommendations of adjuvant therapy for node-negative invasive breast cancer in Japanese patients.

BACKGROUND: The objectives of this study were to confirm the favorable outcome of invasive breast cancer in Japanese patients without lymph node metastasis who did not receive adjuvant therapies and to validate the St-Gallen recommendations in this population. METHODS: The subjects were a consecutive series of 920 node-negative invasive breast cancer patients who underwent surgery between 1987 and 1994 at our hospital. These patients did not receive adjuvant chemotherapy. Ten-year disease-free (DFS) and overall survival (OS) rates were analyzed by the St-Gallen risk categories (Minimal/Low, Intermediate, High). RESULTS: The median age of the patients at surgery was 52 years and the median follow-up period of patients was 10.2 years. At 10 years, the respective DFS and OS rates of all patients were 84.6 and 86.7%. The DFS and OS of patients in the Minimal/Low risk category (25 patients) both showed 100%. The DFS and OS of patients in the Intermediate risk category (356 patients) showed 92.0 and 93.1%, respectively. The DFS and OS of patients in the High risk category (539 patients) showed 79.4 and 82.2%, respectively, indicating a significant difference between those in the Minimal/Intermediate risk category (381 patients) (p < 0.001, p < 0.001, respectively). The DFS and OS of patients who had one pathological lymph node metastasis (775 patients) showed 72.7 and 75.2%, respectively, which indicated a non-significant difference between those in the High risk category (381 patients) (p = 0.10). These data support the validation of adjuvant therapy for high-risk node-negative breast cancers in Japanese patients. However, quality control is needed to define the histological grade included in the risk categories. CONCLUSION: Japanese patients with invasive breast cancer without lymph node metastasis showed a survival advantage compared with their Caucasian counterparts. However, patients in the High risk group as defined by St-Gallen recommendations should be indicated for adjuvant therapy.     

Metformin and thiazolidinediones are associated with improved breast cancer-specific survival of diabetic women with HER2+ breast cancer

BackgroundInsulin/insulin-like growth factor-I (IGF-I) signaling is a mechanism mediating the promoting effect of type 2 diabetes (DM2) on cancer. Human epidermal growth factor receptor (HER2), insulin receptor and IGF-I receptor involve the same PI3K/AKT/mTOR signaling, and different antidiabetic pharmacotherapy may differentially affect this pathway, leading to different prognoses of HER2+ breast cancer.MethodsWe reviewed 1983 consecutive patients with HER2+ breast cancer treated between 1 January 1998 and 30 September 2010. The overall survival, breast cancer-specific death rate, age, race, nuclear grade, stage, menopausal status, estrogen and progesterone receptor status, body mass index and classes of antidiabetic pharmacotherapy were analyzed.ResultsA Cox regression analysis showed that DM2 [P = 0.026, hazard ratio (HR) = 1.42, 95 % confidence interval (95 % CI) 1.04–1.94] predicted poor survival of stage ≥2 HER2+ breast cancer. In Kaplan–Meier analysis, metformin predicted lengthened survival and so did thiazolidinediones. Analyzing only the diabetics, Cox regression showed that metformin (P = 0.041, HR = 0.52, 95 % CI 0.28–0.97) and thiazolidinediones (P = 0.036; HR = 0.41, 95 % CI 0.18–0.93) predicted lengthened survival, and competing risk analysis showed that metformin and thiazolidinediones were associated with decreased breast cancer-specific mortality (P = 0.023, HR = 0.47, 95 % CI 0.24–0.90 and P = 0.044, HR = 0.42, 95 % CI 0.18–0.98, respectively).ConclusionsThiazolidinediones and metformin users are associated with better clinical outcomes than nonusers in diabetics with stage ≥2 HER2+ breast cancer. The choice of antidiabetic pharmacotherapy may influence prognosis of this group.     

Swiss adjuvant trials in women with node-negative breast cancer. OSAKO.

Women with node-negative breast cancer have a 30% chance of relapse 5 years after mastectomy. If it is possible to prevent or defer recurrent disease with adjuvant systemic therapy, node-negative patients, with their low tumor burden, should theoretically benefit most from such treatment. In 1974 we started a randomized adjuvant trial in eastern Switzerland, using a subjectively less toxic regimen [chlorambucil, methotrexate, and fluorouracil (LMF)]. Two hundred fifty-four patients were randomly assigned after standardized modified radical mastectomy to observation only or to treatment with oral LMF for 6 months followed by BCG skin scarifications monthly for up to 2 years. While we find no significant statistical difference between the control group and the treated group in terms of relapse-free survival, there is a strong and consistent trend toward prolongation of overall survival within the treated group.     

High expression of 90K (Mac-2 BP) is associated with poor survival in node-negative breast cancer patients not receiving adjuvant systemic therapies

90K (Mac-2 BP) expression was evaluated by immunohistochemistry in paraffin-embedded tissue from a consecutive series of lymph-node negative breast cancer patients who did not receive adjuvant systemic treatment. An independent series of patients served as validation set. The association of 90K expression with risk of recurrence and death was examined in survival analyses together with known prognostic factors. High levels of 90K expression (IHC score>8) were observed in 43 (25.3%) of 170 tumors examined. We found elevated risks of distant recurrence and overall mortality in patients with high 90K expression compared with patients with low 90K expression in their tumors. This increase persisted after adjusting for other prognostic factors in multivariate analysis (hazard ratio=4.084; p<0.001 for recurrence; hazard ratio=4.298; p<0.001 for death). These findings were confirmed in the validation set. Therefore, evaluation of 90K expression may be beneficial to identify lymph-node negative breast cancer patients at lower risk of disease recurrence and death.     

The combination of p53 mutation and neu/erbB-2 amplification is associated with poor survival in node-negative breast cancer.

PURPOSE: Increases in neu/erbB-2 have been implicated in breast cancer prognosis, but do not predict all recurrences. On the basis of evidence that p53 mutation is involved in the development of human neoplasia, we examined the prognostic value of p53 alterations in combination with neu/erbB-2 amplification. PATIENTS AND METHODS: A consecutive series of women were observed for recurrence and death (median follow-up of 85 months) and tumors from 543 individuals were analyzed for p53 mutation status and neu/erbB-2 amplification. Exons 4 through 10 of the p53 gene were analyzed by single-stranded conformational polymorphism and mutations were confirmed by DNA sequencing. The association of p53 mutation status and neu/erbB-2 amplification with risk of recurrence and death was examined in survival analyses with traditional and histologic markers as prognostic factors. RESULTS: p53 mutations occurred in 24.5% of the axillary node-negative breast carcinomas. Mutations were more frequent in carcinomas with neu/erbB-2 amplification: 38.9% compared with only 20.9% in those without neu/erbB-2 amplification. We found elevated risks of disease recurrence and overall mortality in patients with both p53 mutation and neu/erbB-2 amplification in their tumor compared with patients with neither or only one of the alterations. This increase persisted with adjustment for other prognostic factors (relative risk, 2.32; P =.002 for recurrence; relative risk, 2.22; P =.004 for death). CONCLUSION: Evaluation of tumors for p53 mutations may be beneficial to identify women at higher risk of disease recurrence and death when the tumor has neu/erbB-2 amplification, but in the absence of neu/erbB-2 amplification, the presence of p53 mutation may not provide additional independent prognostic information.     

Postmastectomy radiation therapy and recommendations for immediate breast reconstruction in women with stage II breast cancer

Recent developments in management have demonstrated superior local-regional control, disease-free survival, and overall survival in node-positive breast cancer patients with the addition of postmastectomy radiation therapy (PMRT) to mastectomy and chemotherapy. Consequently, PMRT use in patients with stage II breast cancer is increasing. However, it is difficult to predict presence or extent of axillary lymph node involvement before mastectomy. There are two potential problems with performing an immediate breast reconstruction in patients requiring PMRT. First, PMRT may adversely affect the aesthetic outcome of an immediate breast reconstruction. Second, immediate breast reconstruction may interfere with PMRT delivery. With a delayed-immediate approach, however, patients who do not require PMRT may achieve aesthetic outcomes similar to those with immediate reconstruction. In patients requiring PMRT, delayed-immediate breast reconstruction may avoid potential aesthetic and radiation delivery problems after immediate breast reconstruction. Increased PMRT use in early-stage breast cancer requires improved communication among the medical oncologist, radiation oncologist, breast surgeon, and plastic surgeon during treatment planning.     

Adjuvant systemic therapy for lymph node-negative breast cancer less than or equal to 1 cm

Routine screening mammography has increased the incidence of stage I breast cancers. Many more women are being diagnosed with lymph node-negative tumors that are less than or equal to 1 cm in greatest diameter. The National Surgical Adjuvant Breast and Bowel Project recently performed a retrospective analysis of 10,302 women participating in one of five clinical trials, including women with lymph node-negative breast cancer. Of these women, 1259 had tumors less than or equal to 1 cm. The analysis of the women with tumors less than or equal to 1 cm revealed an improved relapse-free survival (RFS) if tamoxifen was given after surgery, compared with surgery alone, for women with estrogen receptor (ER)-positive tumors; and for women with ER-negative tumors, RFS was improved by delivering chemotherapy after surgery. The authors suggested that adjuvant systemic therapy should be considered for anyone with an invasive breast cancer, regardless of the size of the tumor. This paper reviews the data presented in that important, historic article, and discusses their conclusions. Also reviewed are the most recent recommendations for treatment of primary breast cancer from the International Consensus Panel that convened at the Seventh International Conference on Adjuvant Therapy of Primary Breast Cancer in St. Gallen, Switzerland. That panel also addressed the issue of adjuvant systemic therapy in women considered to have a minimal or low risk of developing recurrent disease.     

Trends in breast cancer treatment in Korea and impact of compliance with consensus recommendations on survival

Although some studies suggest that conformity with consensus recommendations for breast cancer therapy is associated with increased survival, the data are not clear. We identified patients in four hospital-based breast cancer registries in Korea who had undergone primary curative surgery (stage 0–III) from 1993 through 2002 (n = 8,407). We collected demographic and clinical characteristics such as age, stage, treatment, and hormone receptor status. We gathered 1993–2004 mortality data by linkage to the National Statistical Office. During the follow-up period of 43,145 person–years (mean, 5.13 years), we identified 899 deceased cases. We used the standard Poisson regression model to estimate the hazard ratio (HR) for survival in relation to conformity with guidelines for chemo-, hormone, and locoregional therapy. Guideline compliance for systemic therapy increased from 24.0% in 1993 to 83.8% in 2002. Among mastectomy patients with <4 positive lymph nodes and tumors <5 cm, post-mastectomy radiotherapy was associated with poor survival (HR 2.07; 95% CI: 1.53–2.81). Tamoxifen use was associated with better survival among patients with hormone receptor-positive tumors (HR 0.57; 95% CI: 0.45–0.73) and with poorer survival among hormone receptor-negative patients who had affected nodes (HR 1.58; 95% CI: 1.01–2.44). Relative to conformity, non-conformity with both chemo- and hormone therapy guidelines was associated with a 76% higher risk of death. Compliance with consensus recommendations for chemo- and hormone therapy is significantly associated with better survival. Overuse of post-mastectomy radiotherapy and tamoxifen beyond the consensus recommendations may be harmful. Young Ho Yun and Sang Min Park contributed equally to this work as first authors.