Effect of Large Tumor Size on Cancer-Specific Mortality in Node-Negative Breast Cancer

Department of Breast Surgery, Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China. Electronic address: .
Mayo Clinic Proceedings (Impact Factor: 6.26). 12/2012; 87(12):1171-1180. DOI: 10.1016/j.mayocp.2012.07.023
Source: PubMed


To examine the relationship between large tumor size and breast cancer-specific mortality (BCSM), especially in a subset of patients with negative lymph nodes (LNs).

Patients and methods:
We used the Surveillance, Epidemiology and End Results registry to identify 107,705 female patients diagnosed from January 1, 1990, through December 31, 2003, as having invasive breast cancer and treated with surgery and LN dissection. Relevant issues unclear in the database were studied in an additional 335 patients with locally advanced disease treated with neoadjuvant chemotherapy.

In the multivariable analysis, a significant interaction was found between tumor size and LN involvement (P<.001). In LN-negative diseases, the relationship between tumor size and BCSM was piecewise. Using 21- to 30-mm tumors as the reference, the hazard ratio (HR) of BCSM increased with increasing tumor size until a peak at 41 to 50 mm (HR, 1.49; P<.001), after which increasing tumor size was unexpectedly related to decreasing hazard, with a nadir at 61 to 80 mm (HR, 1.06; P=.70). The 61- to 80-mm tumors exhibited a significantly lower BCSM compared with the 41- to 50-mm (P=.02) and greater than 80-mm (P=.03) subgroups. This pattern remained after stratification by estrogen receptor status but was not observed in patients with LN-positive disease. Further analysis indicated that the survival advantage of 61- to 80-mm tumors in LN-negative disease might result from its low risk of distant metastasis.

A relatively larger tumor size without LN involvement may be a surrogate for biologically indolent disease of distant metastasis. Our findings, if validated in other large databases, may provide better understanding of breast cancer biology.

Download full-text


Available from: Yizhou Jiang, Dec 30, 2013
30 Reads
  • Source
    • "Third, at least 57% of all the study patients (according to Hershman’s [6] and Nurgaliev’s [20] studies) were older than 65 years. The different age distribution of the patients between this study and general breast cancer population (median age is 55 years according to SEER database [35]) might have potential impacts on the conclusion. Fourth, our study relies on the assumption of a log-linear relationship for the effect of waiting time on survival. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Adjuvant chemotherapy (AC) improves survival among patients with operable breast cancer. However, the effect of delay in AC initiation on survival is unclear. We performed a systematic review and meta-analysis to determine the relationship between time to AC and survival outcomes. Methods PubMed, EMBASE, Cochrane Database of Systematic Reviews, and Web-of-Science databases (between January-1 1978 and January-29, 2013) were searched for eligible studies. Hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) from each study were converted to a regression coefficient (β) corresponding to a continuous representation per 4-week delay of AC. Most used regimens of chemotherapy in included studies were CMF (cyclophosphamide, methotrexate, and fluorouracil) or anthracycline-based. Individual adjusted β were combined using a fixed-effects or random-effects model depending on heterogeneity. Results We included 7 eligible studies with 9 independent analytical groups involving 34,097 patients, 1 prospective observational study, 2 secondary analyses in randomized trials (4 analytical groups), and 4 hospital-/population-based retrospective study. The overall meta-analysis demonstrated that a 4-week increase in time to AC was associated with a significant decrease in both OS (HR = 1.15; 95% confidence interval [CI], 1.03-1.28; random-effects model) and DFS (HR = 1.16; 95% CI, 1.01-1.33; fixed-effects model). One study caused a significant between-study heterogeneity for OS (P < 0.001; I2 = 75.4%); after excluding that single study, there was no heterogeneity (P = 0.257; I2 = 23.6%) and the HR was more significant (HR = 1.17; 95% CI, 1.12-1.22; fixed-effects model). Each single study did not fundamentally influence the positive outcome and no evidence of publication bias was observed in OS. Conclusions Longer time to AC is probably associated with worse survival in breast cancer patients.
    BMC Cancer 05/2013; 13(1):240. DOI:10.1186/1471-2407-13-240 · 3.36 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Node-negative breast cancers from 2 cm to 5 cm in size are classified as stage ii, and smaller cancers, as stage i. We sought to determine if the prognosis of women with a breast cancer exactly 2 cm in size more closely resembles that of women with a stage i or a stage ii breast cancer. Using a cohort of 4265 young women with breast cancer, we compared the 10-year breast cancer mortality rates for women who had a tumour 0.1-1.9 cm, exactly 2.0 cm, and 2.1-2.9 cm. In the first 3 years after diagnosis, the survival pattern of women with a 2.0-cm breast cancer was nearly identical to that of women with a larger cancer (2.1-3.0 cm). From year 3 to year 10, the relative survival of women with a 2.0-cm breast cancer was improved and nearly identical to that of women with a smaller cancer. The 10-year survival rate was 89.3% for women with tumours less than 20 mm, 86.1% for women with tumours equal to 20 mm, and 81.2% for women with 21-mm to 29-mm tumours. For young women with small breast cancers, the relative mortality from breast cancer is dynamic with increasing tumour size and varies with time from diagnosis.
    Current Oncology 08/2013; 20(4):205-11. DOI:10.3747/co.20.1364 · 1.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Sexually transmitted infection with the human papillomavirus (hpv) is responsible for a significant burden of human cancers involving the cervix, anogenital tract, and oropharynx. Studies in the United States and Europe have demonstrated an alarming increase in the frequency of hpv-positive oropharyngeal cancer, but the same direct evidence does not exist in Canada. Using the London Health Sciences Centre pathology database, we identified tonsillar cancers diagnosed between 1993 and 2011. Real-time polymerase chain reaction was then used on pre-treatment primary-site biopsy samples to test for dna from the high-risk hpv types 16 and 18. The study cohort was divided into three time periods: 1993-1999, 2000-2005, and 2006-2011. Of 160 tumour samples identified, 91 (57%) were positive for hpv 16. The total number of tonsillar cancers significantly increased from 1993-1999 to 2006-2011 (32 vs. 68), and the proportion of cases that were hpv-positive substantially increased (25% vs. 62%, p < 0.002). Those changes were associated with a marked improvement in 5-year overall survival (39% in 1993-1999 vs. 84% in 2006-2011, p < 0.001). When all factors were included in a multivariable model, only hpv status predicted treatment outcome. The present study is the first to provide direct evidence that hpv-related oropharyngeal cancer is increasing in incidence in a Canadian population. Given the long lag time between hpv infection and clinically apparent malignancy, oropharyngeal cancer will be a significant clinical problem for the foreseeable future despite vaccination efforts.
    Current Oncology 08/2013; 20(4):212-9. DOI:10.3747/co.20.1375 · 1.79 Impact Factor
Show more