Postmastectomy Reconstruction Is Associated with Improved Survival in Patients with Invasive Breast Cancer: A Single-institution Study

Breast reconstruction after mastectomy positively affects psychosocial well-being; however, the influence of reconstruction on cancer outcomes is unknown. The objective of our study was to compare survival in reconstructed versus nonreconstructed patients after mastectomy. All consecutive female patients diagnosed with invasive breast cancer and treated with mastectomy between 2002 and 2011 were identified from our single-institution database. All cancer operations were performed by two surgeons. Survival was calculated using the Kaplan-Meier method and compared using the log-rank test. To identify the effect of reconstruction on survival, a multivariate Cox regression analysis was performed. Of 474 patients treated, 340 (71.7%) underwent breast reconstruction. At a mean follow-up 3.3 years, reconstructed patients had a longer 5-year survival (91 vs 74%, P < 0.001). After controlling for age, race, payer source, cancer stage, triple negative status, and receipt of radiation or chemotherapy, reconstructed patients maintained a survival advantage over nonreconstructed patients (hazard ratio, 0.47; 95% confidence interval, 0.25 to 0.88; P = 0.02). Patients with breast cancer who undergo reconstruction have longer survival than nonreconstructed patients. The explanation for this finding may be related to improved psychosocial qualities of life versus possible antitumorigenic effects of implants.

THE SURGICAL MANAGEMENT of breast cancer continues to evolve as surgeons seek to minimize breast disfigurement and morbidity while maintaining oncologic safety. To this end, breast conservation surgery became the preferred treatment for early-stage breast cancer after studies proved equivalent survival compared with mastectomy,1 thus allowing surgeons to safely maintain the natural breast mound. However, despite this initial trend toward breast conservation, there has been an increase in mastectomy rates over the past decade and recent studies estimate nearly half of patients with early-stage breast cancer are undergoing mastectomy.2-4 For these patients who require or elect for mastectomy, breast reconstruction is an important part of their surgical care. It is known that the disfigurement associated with mastectomy negatively affects body image and sexual function and surgically conserving or restoring the breast mound enhances the psychosocial quality of life in patients undergoing mastectomy.5-9 However, there may be more benefit to reconstruction that is yet to be identified. Recent population-level data suggested a survival benefit for reconstructed patients compared with patients undergoingmastectomy without reconstruction10-13 and there is research to suggest possible anticarcinogenic effects of implant reconstruction.14, 15 Although these findings are intriguing, they are based on a few populationlevel studies with overall low reconstruction rates. Therefore, further investigations are needed to confirm a causal role of reconstruction on improved breast cancer outcomes and survival. Nearly all patients at our institution are offered postmastectomy reconstruction, resulting in a reconstruction rate of 70 per cent, which is nearly triple the modern rates reported in national databases (15 to 25%).16, 17 Thus, our breast cancer patient population represents an ideal cohort for studying differences related to reconstruction. We therefore sought to evaluate overall survival in patients who underwent immediate or delayed breast reconstruction at our institution.

Methods

Database

The University of California San Diego Moores Cancer Center (UCSD-MCC) cancer registry is a prospectively managed database that collects demographic, oncologic, and treatment-related data on all breast cancer patients treated at UCSD since 1998. Follow-up information was updated through June 2011 at the time of our study.

Study Population

After obtaining Institutional Review Board approval, we queried the database using site-specific procedure codes to identify all consecutive female patients with breast cancer treated with unilateral or bilateral mastectomy between 2002 and 2011. We began our study analysis in 2002 because electronic records were available starting in this year and this was necessary for supplemental chart review of our study population. Patients with a histologic-confirmed diagnosis of invasive breast cancer were included. Male patients and patients with the diagnosis of ductal carcinoma in situ (DCIS) were excluded from analysis. Bilateral mastectomy was defined as bilateral mastectomy in the setting of unilateral cancer. Patients who underwent bilateral mastectomies for bilateral cancers were treated as individual cases and coded as unilateral mastectomy. Reconstruction was defined as receiving autologousbased reconstruction, implant-based, or both (e.g., latissimus flap with implant) at any time after mastectomy.

Demographic and tumor characteristics were collected for study patients from the UCSD-MCC cancer registry and supplemented with additional retrospective chart review, as necessary. Demographic information included year of diagnosis, age at diagnosis (younger than 40, 41 to 64, older than 65 years), race (white, black, Asian, or Hispanic), and payer source (private insurance, Medicare, public assistance [e.g., Medicaid], or uninsured/other). Cancer-specific data included cancer stage (I to IV according to the American Joint Committee on Cancer staging scheme, second edition), histologic subtype (ductal, lobular, mixed, tubular), estrogen receptor/progestin receptor (ER/PR) status, human epidermal growth factor receptor 2 (HER2) status, and presence of lymphovascular invasion (LVI). Lymph node status was reported as zero, one to three, or more than three positive regional lymph nodes. Triple negative status was assigned as ER, PR, and HER2 negativity. Adjuvant treatment data included receipt of postmastectomy radiation and/or chemotherapy. Cancer recurrence was defined as positive or negative at the time of last follow-up. Survival time was recorded from the time of breast cancer diagnosis to the time of death or date of last follow-up and recorded in terms of months.

Statistical Analysis

The primary outcome of our study was overall survival. Patients were grouped according to mastectomy with reconstruction or mastectomy without reconstruction. Demographic and tumor-specific data were categorized into ordinal groups and compared using the x2 test. Survival times were calculated using the Kaplan-Meier method from the date of diagnosis to the date of death or date of last follow-up. The logrank test was used to compare the equality of survival curves. A multivariate Cox proportional hazards model controlling for demographic (age, race, payer source) and cancer-specific (stage, presence of LVI, triple negative disease, adjuvant treatment) covariates was performed and presented as hazard ratios (HRs) with 95 per cent confidence intervals (CIs). All statistical tests were two-sided, and P values < 0.05 were considered statistically significant. SPSS software was used for all analysis (Version 12; Chicago, IL).

Results

Patient Characteristics

Of the 1716 patients treated for breast cancer at UCSD-MCC over our study period, 626 (36.5%) underwent mastectomy. We excluded 141 patients with DCIS and eight patients based on male sex. The remaining 474 female patients treated with mastectomy for invasive breast cancer during our study period comprised our study population. Demographic and tumor characteristics are described in Table 1. The majority of patients were white, age 41 to 64 years, and had ER/PR-positive tumors with ductal histology.

Comparison of the Reconstructed and Nonreconstructed Cohorts

Of the 474 study patients, 340 (71.7%) underwent breast reconstruction, whereas 134 (28.3%) underwent mastectomy alone. Of the reconstructed women, 320 (94%) underwent immediate breast reconstruction. Women who underwent breast reconstruction were more likely to be younger, have private payer insurance, and undergo bilateral mastectomy compared with women who underwent mastectomy alone. Reconstructed and nonreconstructed patients were similar in all measured oncologic characteristics including stage, histologic subtype, lymph node status, presence of LVI, and hormone status. Reconstruction status did not affect whether a patient underwent adjuvant radiation or chemotherapy.

Survival Analysis

At mean follow-up of 3.4 and 3.3 years for the reconstructed and nonreconstructed cohorts, respectively, overall survival was significantly longer in the reconstructed cohort (mean survival 11.2 vs 8.5 years; 3-year survival 94 vs 81%; P < 0.001) (Fig. 1).

On multivariate analysis (Table 2), after controlling for age, race, payer source, cancer stage, receipt of chemotherapy, adjuvant radiotherapy, triple negative disease status, and presence of LVI, reconstruction status was an independent predictor of survival (HR, 0.47; 95% CI, 0.25 to 0.88; P40.02). Triple negative disease and advanced cancer stage were also independent predictors of survival (HR, 3.60; 95% CI, 1.84 to 7.05; P < .001 and HR, 5.12; 95% CI, 1.61 to 16.2; P 4 0.01, respectively).

Discussion

Our finding of improved survival in reconstructed patients is consistent with recent population-level studies. An analysis of the Surveillance, Epidemiology and End Results (SEER) data evaluating 52,000 female patients diagnosed with breast cancer between 1998 and 2002 demonstrated longer survival times in reconstructed patients compared with patients undergoing mastectomy alone, even after controlling for other clinicopathologic factors.12 Three additional analyses of SEER data from similar time periods, but with slightly different inclusion criteria, all report improved breast cancer-specific survival among reconstructed patients.10, 11, 13 The Danish Breast Cancer Cooperative Group found the same trend with significantly improved disease-free survival and a nonsignificant increase in overall survival in the reconstructed population.18

Although collectively these studies provide convincing evidence that reconstruction may be playing a role in improved survival, population-level studies are limited by surgeon selection bias that may be reconstructing a healthier population that lives longer based on tumor characteristics regardless of their reconstruction status. Despite an attempt to promote reconstruction with passage of the Women's Health and Cancer Rights Act implemented in 1999, a continued disparate use of reconstruction exists nationally, particularly for patients of higher socioeconomic status and favorable tumor characteristics.16, 19-21 However, our findings are less likely to be influenced by a surgeon selection bias, because our two-surgeon oncologic breast team at UCSD-MCC nondiscriminantly offers reconstruction to all eligible patients undergoing mastectomy and all patients receive treatment with the same institutional standards. This is exemplified by our reconstruction rate of 71.7 per cent and the similarity of patient characteristics between our nonreconstructed and reconstructed cohorts (Table 1). Both cohorts were similar in cancer stage, tumor grade, regional lymph node status, and presence of LVI. Our finding of improved survival in reconstructed patients provides additional support to prior studies suggesting reconstruction may play a role in improving breast cancer outcomes.

The survival benefit for reconstructed patients may be related to a protective effect of implant reconstruction. A survival analysis of reconstructed patients stratified by reconstruction type found a greater survival advantage in young patients undergoing implant reconstruction over use of autologous tissue only.10 Further evidence from the Los Angeles Augmentation Mammaplasty study, which followed over 50,000 women who underwent noncancer-related cosmetic breast implants for 17 years, found these women had a lower incidence of breast cancer than expected of the general population.22 Some studies support a biological mechanism for this finding, postulating that breast implants may create a hostile tissue environment retarding cancer growth by stimulating a local immune response or by means of physically compressing breast tissue, which impairs blood flow to any potential or surviving cancer cells.14, 15

Another possible explanation for our finding is the psychosocial benefit realized in the reconstructed population may be translating into a survival advantage. In a study evaluating the psychosocial predictors of survival in patients with breast cancer, a minimizing coping style (e.g., minimizing the impact of cancer diagnosis) was the most significant independent predictor of survival.23 Surgically restoring the breast mound to re-establish a pretreatment body image may minimize the perceived impact of breast cancer diagnosis among reconstructed patients, thus conferring a survival advantage.

Limitations to our study include that it is retrospective with a relatively short follow-up. Additionally, although our preferred method of reconstruction is tissue expander implant-based or combined autologous and implant-based reconstruction, we did not stratify our population by type of reconstruction so we cannot determine how reconstruction method affects survival. Our study contributes to prior studies by its single-institution design and relatively large population undergoing reconstruction.

Conclusion

An analysis of patients with invasive breast cancer treated at our institution demonstrates longer survival times for those undergoing reconstruction versus nonreconstructed ones. We have postulated several reasons for this association including possible psychosocial benefit translating into a survival advantage versus antitumorigenic effects of breast implants versus other. Although the exact mechanism is unclear, the results from our study further support the growing amount of data suggesting oncologic benefits to breast reconstruction.

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JENNIFER L. BAKER, M.D.,* BRIAN MAILEY, M.D.,*[double dagger] CHRISTOPHER A. TOKIN, M.D.,* SARAH L. BLAIR, M.D.,*[dagger] ANNE M. WALLACE, M.D.*[dagger][double dagger]

From the *Department of Surgery, [dagger]Division of Surgical Oncology, and [double dagger]Plastic and Reconstructive Surgery, University of California, San Diego, San Diego, California

Presented at the 24th Annual Scientific Meeting of the Southern California Chapter of the American College of Surgeons, January 18-20, 2013, in Santa Barbara, California.

Address correspondence and reprint requests to Jennifer L Baker, M.D., Resident, Department of General Surgery, 200 W. Arbor Drive, San Diego, CA 92103. E-mail: [email protected].