Clinical Investigation
Local Recurrence in Women With Stage I Breast Cancer: Declining Rates Over Time in a Large, Population-Based Cohort

Presented in part at the Canadian Association of Radiation Oncologists Annual Meeting, Ottawa, Ontario, Canada, September 12-15, 2012.
https://doi.org/10.1016/j.ijrobp.2013.10.001Get rights and content

Purpose

To evaluate whether local recurrence (LR) risk has changed over time among women with stage I breast cancer treated with breast-conserving therapy.

Methods and Materials

Subjects were 5974 women aged ≥50 years diagnosis with pT1N0 breast cancer from 1989 to 2006, treated with breast-conserving surgery and radiation therapy. Clinicopathologic characteristics, treatment, and LR outcomes were compared among 4 cohorts stratified by year of diagnosis: 1989 to 1993 (n=1077), 1994 to 1998 (n=1633), 1999 to 2002 (n=1622), and 2003 to 2006 (n=1642). Multivariable analysis was performed, with year of diagnosis as a continuous variable.

Results

Median follow-up time was 8.6 years. Among patients diagnosed in 1989 to 1993, 1994 to 1998, 1999 to 2002, and 2003 to 2006, the proportions of grade 1 tumors increased (16% vs 29% vs 40% vs 39%, respectively, P<.001). Surgical margin clearance rates increased from 82% to 93% to 95% and 88%, respectively (P<.001). Over time, the proportions of unknown estrogen receptor (ER) status decreased (29% vs 10% vs 1.2% vs 0.5%, respectively, P<.001), whereas ER-positive tumors increased (56% vs 77% vs 86% vs 86%, respectively, P<.001). Hormone therapy use increased (23% vs 23% vs 62% vs 73%, respectively, P<.001), and chemotherapy use increased (2% vs 5% vs 10% vs 13%, respectively, P<.001). The 5-year cumulative incidence rates of LR over the 4 time periods were 2.8% vs 1.7% vs 0.9% vs 0.8%, respectively (Gray's test, P<.001). On competing risk multivariable analysis, year of diagnosis was significantly associated with decreased LR (hazard ratio, 0.92 per year, P=.0003). Relative to grade 1 histology, grades 2, 3, and unknown were associated with increased LR. Hormone therapy use was associated with reduced LR.

Conclusion

Significant changes in the multimodality management of stage I breast cancer have occurred over the past 2 decades. More favorable-risk tumors were diagnosed, and margin clearance and systemic therapy use increased. These changes contributed to the observed declining LR rates among patients treated with breast-conserving therapy.

Introduction

Breast-conserving therapy is the standard of care for most women with early stage breast cancer. After breast-conserving surgery, whole-breast radiation therapy (RT) has been shown in randomized trials and meta-analyses to improve local control and provide survival rates similar to those of mastectomy 1, 2, 3, 4. Advances in breast cancer screening, surgical techniques, and adjuvant therapy have improved local control and survival in patients with early-stage breast cancer. Increased awareness and use of mammographic screening have contributed to earlier diagnoses of smaller tumors. Improved surgical technique and pathologic evaluation have led to more accurate margin assessments and assignment of pathologic stages (5).

Prospective trials 6, 7 and single-institution series 8, 9 have emerged with reports of declining local recurrence (LR) rates after breast-conserving therapy in women with early stage breast cancer. In a United Kingdom trial examining 1410 women with T1-3 N0-1 M0 breast cancer treated with breast-conserving surgery and radiation therapy between 1986 and 1998, 5-year LR was 8% (95% confidence interval [CI], 6.5%-9.5%) (6). In contrast, a more contemporary UK trial testing fractionation regimens in 4451 women between 1998 and 2002 reported a lower 5-year LR rate of 3.1% (95% CI, 2.6%-3.7%) (7). While these findings suggest that LR risks may be diminishing over time, comparisons among different studies are limited by variations in diagnostic, surgical, pathologic or stage distribution that could influence LR risk trends.

This study examined whether local recurrence risk has changed over time among women consecutively diagnosed with stage I breast cancer treated with breast-conserving surgery and RT, using population-based data from a Canadian provincial cancer institution.

Section snippets

Study subjects

An institutional database with prospectively collected information on demographics, treatment, and outcomes in referred patients was used to identify the subjects of this analysis. The study cohort included 5974 women aged ≥50 years diagnosed with pT1N0 invasive breast cancer between 1989 and 2006. All patients were treated with breast-conserving surgery and adjuvant breast RT. The study excluded patients with in situ breast cancer, node-positive disease, unknown nodal status, distant

Results

The median follow-up time was 8.6 years. Table 1 summarizes data comparing clinicopathologic characteristics among the 4 time periods. The mean age at diagnosis was similar in the 4 cohorts. The mean tumor size was similar among cohorts. Among patients diagnosed in 1989 to 1993, 1994 to 1998, 1999 to 2002, and 2003 to 2006, the proportions of grade 1 tumors increased over time (16% vs 29% vs 40% vs 39%, respectively, P<.001). Rates of LVI declined over the 4 time periods (20% vs 10% vs 7% vs

Discussion

This longitudinal outcomes study provides documentation that at the population level, LR rates are declining in women with pT1N0 breast cancer treated with breast-conserving therapy. Other institutional series have reported declining LR rates over time. Investigators from the William Beaumont Hospital evaluated patterns of disease recurrence over time from 1981 to 1996 in 607 patients with stages I to II breast cancer treated with breast-conserving surgery and RT. Reduced 5-year and 12-year LR

Conclusions

Significant changes in tumor characteristics, surgical techniques, and adjuvant systemic therapy for breast cancer have occurred over the past 2 decades. This has resulted in the diagnoses of more favorable risk tumors, higher rates of margin clearance, and increased systemic therapy use. These changes contribute to the observed declining rates of LR at the population level among women with early stage breast cancer treated with breast-conserving surgery and radiation therapy.

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    Conflict of interest: none.

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