Abstract
Introduction
Breast cancer is the most commonly diagnosed cancer among women in the general U.S. population and within the Military Health System (MHS).1-3 Age at diagnosis is a known factor influencing breast cancer presentation, treatment, and outcomes.4-7 Younger premenopausal women are more likely to present with aggressive tumor subtypes, such as triple-negative or HER2-positive disease, and often receive more intensive treatment, including neoadjuvant chemotherapy and bilateral mastectomy.4,8-10 In contrast, older postmenopausal women are more likely to present with estrogen-receptor positive disease, have less aggressive subtypes, and may have lower rates of surgery and adjuvant therapy due to concerns about comorbidity, frailty, or competing mortality risks.11-14 These patterns contribute to age-related disparities in breast cancer outcomes, including lower breast cancer-specific survival among women aged ≥75 years, even when controlling for tumor subtype and stage.10,15-17
Surgical treatment—either breast-conserving therapy (BCT) or mastectomy—remains a cornerstone of curative-intent management for patients of all ages with nonmetastatic disease. 18 However, short-term postoperative complications can delay adjuvant therapies, prolong recovery, and adversely affect both quality of life and long-term outcomes.19-21 Little is known about how age affects short-term surgical outcomes, particularly postoperative complications. Prior studies have reported conflicting findings, with some showing no significant differences by age, while others have observed elevated medical complication risks in older patients, especially following mastectomy.22-25 Younger patients may also be at increased risk of postoperative morbidity and reoperation due to more extensive surgical procedures or additional interventions.5,20
In the general U.S. population, access to cancer screening, diagnosis, and treatment services may vary between age groups based on insurance coverage and financial barriers.26-29 Research in a universal care system can minimize many of the socioeconomic barriers that complicate care and research in the general U.S. population and help inform clinical decision-making and age-appropriate perioperative care.30-32 The MHS serves 9.6 million Department of War (DoW) beneficiaries, including active-duty uniformed service members, retired military service members, activated National Guard, other DoW employees, and their family members. 32 Insurance coverage and access to care is provided to beneficiaries of all ages with low to no out-of-pocket costs. 31 Therefore, the MHS provides a unique setting to examine these associations due to its universal insurance coverage and relatively standardized access to care. This study aimed to examine the association between age at diagnosis and 30-day postoperative outcomes including general and breast-specific complications and hospital readmissions among women undergoing surgery without immediate reconstruction for stage I–III breast cancer in the MHS.
Materials and Methods
Data Sources
This study used the MilCanEpi database which contains information on patients diagnosed or treated for cancer in the MHS from the DoW cancer registry linked to administrative data and medical encounters in the MHS data repository employing similar methods as Eaglehouse et al.33,34 The study was reviewed and informed consent was waived by the Uniformed Services University of the Health Sciences Institutional Review Board, Bethesda, Maryland (FWA 00001628) on 19 July 2019 (Reference #914142) and renewed on 4 March 2025 (Reference #981045). The study was conducted in accordance with the Helsinki Declaration of 1975, as revised in 2024. The Reporting of studies Conducted using Observational Routinely-collected health Data (RECORD) checklist was used in the creation of this report. 35
Study Population
The study included women aged ≥18 who were diagnosed with a single primary invasive breast cancer (ICD-O-3 primary site code C500-506, C508, C509 and ICD-9-CM diagnosis codes 174.x) between January 1, 2001 and December 31, 2014 and received surgery as primary treatment. The included data years corresponded with the nationwide expansion of the ACS-NSQIP and the most recent linked data available at the time of analyses.33,36 Women were eligible if they were diagnosed with American Joint Commission on Cancer (AJCC) stages I-III breast cancer and had surgical records in the medical encounter data in MilCanEpi. Patients with stage IV tumors excluded because surgery is not typically delivered as curative treatment. Using methods similar to Eaglehouse et al., 34 breast cancer surgery was defined as any excisional procedure (see Appendix Table A1) within 6 months of the cancer diagnosis. Patients with reconstruction procedures at the time of diagnosis or during follow-up for outcomes were excluded to limit possible effects of reconstruction (eg, approach, timing with surgery) on the measured outcomes.37,38 To reduce unmeasured confounding, patients with surgery recorded only in the cancer registry portion of MilCanEpi were excluded due to incomplete information on study variables.
Study Variables
Patient information included age at diagnosis, race as documented in the data (Asian or Pacific Islander, Black, Native American or Alaska Native, White, multiple races, other race, or unknown), ethnicity (Hispanic, Latinx, or Spanish origin), marital status (married, single, separated, widowed, or divorced), active-duty status at diagnosis (yes or no), sponsor service branch (Air Force, Army, Navy or Marine Corps, or other DoW), U.S. geographic region (Northeast, South, West, or Overseas), and Elixhauser comorbidities modified for those with cancer (0, 1-2, 3-4, or 5 or more).39,40 Comorbidities in the Elixhauser index were captured if there was at least 1 inpatient or 3 outpatient records with a diagnosis code prior to the cancer diagnosis date. Information on recent history of myocardial infarction (MI) within 6 months prior to surgery and chronic heart failure (CHF) within 30 days prior to surgery, as defined in the NSQIP, were also captured.36,41 Patients with recent history of MI or CHF were subsequently excluded due to possible association with the study outcomes.
Cancer information included diagnosis date, AJCC tumor stage (I, II, or III), AJCC tumor grade (G1-4, or Gx), tumor histology (ductal carcinoma, lobular carcinoma, other), tumor laterality (right or left), tumor location (quadrant, nipple or center, overlapping, other), estrogen (ER) and progesterone receptor (PR) status, HER2 status (available 2010-2014), and regional lymph node involvement. Information on cancer surgery included its date, type (partial or breast-conserving mastectomy; or total or radical mastectomy), surgery admission type (inpatient or outpatient), length of stay (LOS) for inpatient surgery admissions, care setting (military or civilian), and final surgical margin (positive or negative). The cancer diagnosis and surgery dates were used to determine time-to-surgery in days. 42 Date(s) of other treatment(s) were extracted from the data to determine whether each patient received neoadjuvant chemotherapy or radiation therapy.
Outcomes
The primary study outcomes included 30-day complications, reoperations, and hospital readmissions. 34 General complications included stroke, myocardial infarction (MI), hemorrhage, blood transfusion, pneumonia, deep vein thrombosis (DVT), pulmonary embolism (PE), other thrombosis, systemic inflammatory response syndrome (SIRS), severe sepsis, septic shock, urinary tract infection (UTI), and death.19,36,38,43-45 Breast complications included surgical site infection (SSI), lymphedema, seroma, and hematoma.19,44,46-51 Medical encounter records with a relevant ICD-9 diagnosis code occurring within 30 days of surgery were used to indicate complications (see Appendix Table A2).19,48,49,52-58 Reoperation included procedures for partial or total mastectomy occurring between 7 and 30 days after the initial surgery. 59 Hospital readmission included inpatient encounters with any diagnosis other than breast reoperation occurring within 30 days of the initial cancer surgery.41,60
Statistical Analysis
First, we examined patients’ characteristics by age at diagnosis, grouped as 18-39, 40-49, 50-64, and ≥65 years using Chi-square tests. The age groups were selected to include women classified as adolescent and young adults (aged 18-39); premenopausal women (aged 40-49), postmenopausal women (aged 50-64), and older women with Medicare eligibility (aged ≥65). We compared the median (interquartile range; IQR) time-to-surgery and median (IQR) LOS for inpatient surgery admission across age groups using non-parametric tests. Then, we reported the frequency of complications, reoperation, and readmissions among age groups and used modified Poisson regression with log link and robust standard errors to estimate rate ratios (RRs) with 95% confidence intervals (CIs) of 30-day outcomes in association with age at diagnosis. Poisson regression was selected because it allows for robust risk estimates for rare (<10%) and non-rare (>10%) events in dynamic cohorts while controlling for potential confounders.61-63 Adjusted rate ratios (ARRs) with 95% CIs were estimated from multivariable models including patient demographic, tumor, and treatment characteristics. Analyses were conducted in SAS 9.4 (SAS Inc., Cary, NC).
Results
The study included 7835 women with a breast cancer diagnosis who received surgery (Figure 1). The average age of women at diagnosis was 56.2 (±12.8) years with 9.2% of women aged 18-39, 23.6% aged 40-49, 42.7% aged 50-64, and 24.5% aged ≥65. A higher proportion of younger women (age 18-39 or 40-49) were non-Hispanic Black race-ethnicity, married, or lived outside the continental United States at time of breast cancer diagnosis relative to women aged 50 or older (Table 1). There was an increasing level of comorbidity with increasing age categories, with women aged ≥65 at diagnosis having the highest frequency of 3-4 comorbidities (23.2%) or ≥5 comorbidities (22.3%) compared to the other age groups. Regarding cancer diagnosis, younger women tended to be diagnosed during earlier years of the data, had a higher frequency of stage II or stage III tumors at diagnosis, had a higher percentage of ductal carcinoma and lower frequency of lobular carcinoma, had higher grade (AJCC G3 or G4), and had a higher frequency of estrogen and progesterone receptor negative tumors relative to older women (Table 2). Selection of patients with stage I-III breast cancer who received surgery without immediate reconstruction as primary treatment in the U.S. Military Health System, 2001-2014 Characteristics of Patients Receiving Primary Surgical Treatment Without Immediate Reconstruction for Stage I-III Invasive Breast Cancer in the U.S. Military Health System, 2001-2014, by Age at Diagnosis aActive-duty status not shown for women ≥65 due to small sample (n < 11) with “yes” value. Breast Cancer Diagnosis and Treatment Information for Patients Receiving Primary Surgical Treatment Without Immediate Reconstruction for Stage I-III Invasive Breast Cancer in the U.S. Military Health System, 2001-2014, by Age at Diagnosis Abbreviations: Estrogen Receptor (ER), Progesterone Receptor (PR). aHER2 status was not a required reporting item in the cancer registry prior to 2010 so it is unavailable for >95% of cancers diagnosed prior to 2010 in the data. bCode for most extensive lymph node surgery in the ±7 days of the primary surgery (partial or total mastectomy); ALND considered most extensive, followed by SLNB, and CFNA.
The median time between cancer diagnosis and surgery in the study cohort was 28 (IQR 16-42) days. The median time-to-surgery increased from 24 days among women aged 18-39 to 30 days among women aged ≥65 (Table 2; Kruskal-Wallis
Overall, 2.0% of the study patients had a general surgical complication and 6.7% had a breast complication. By age, the frequency of general complications differed significantly across age groups (Chi-square Percentage of women with 30-day postoperative complications after receiving surgery for stage I-III breast cancer in the U.S. Military Health System, 2001-2014, by age at diagnosis. Notes. General complications include death, hemorrhage, blood transfusion, myocardial infarction, stroke, urinary tract infection, pneumonia, deep vein thrombosis, pulmonary embolism, other thrombosis, systemic inflammatory response syndrome, severe sepsis, or septic shock; Breast complications include surgical site infection, hematoma, seroma, lymphedema, or upper limb nerve injury; Reoperation is a second surgical procedure (lumpectomy or mastectomy) at least 7 days after the first surgery date and within 30 days of the index surgery; and hospital readmission is any inpatient encounter within 30 days after the initial surgery for any cause, excluding admission related to reoperation. There were n = 0 deaths and n = 0 blood transfusions occurring during the 30-day follow-up Poisson Regression Estimated Adjusted Risk Ratios (ARRs) and 95% Confidence Intervals (CIs) for 30-Day Postoperative Outcomes in Association With Age at Diagnosis Among Women With Stage I-III Breast Cancer Receiving Surgical Treatment Without Immediate Reconstruction
a
in the U.S. Military Health System, 2001-2014 aImmediate reconstruction considered any reconstruction procedure occurring on the date of the initial surgery through 30 days post-op. bPoisson models for ‘general complication’, ‘breast complication’, ‘reoperation’, and ‘hospital readmission’ adjusted for race-ethnicity, marital status, active-duty military status, service branch, geographic region, modified Elixhauser comorbidities, cancer diagnosis year, tumor stage, tumor histology, tumor grade, tumor location, lymph node surgery (sentinel node biopsy or axillary node dissection), lymph node positivity, estrogen and progesterone hormone receptor status, HER2 status (positive, negative, unknown, or unavailable), time-to-surgery, neoadjuvant chemotherapy or radiation, surgery extent (partial or total mastectomy), surgery admission duration (inpatient or outpatient), surgery care setting (military or civilian), and other health insurance. cPoisson models for specific breast complications of ‘surgical site infection’, ‘hematoma’, ‘seroma’, and ‘lymphedema’ adjusted for race-ethnicity, geographic region, comorbidities, tumor stage, tumor histology, tumor location, surgery care setting, surgery type, surgery admission duration, surgery extent, lymph node surgery, lymph node positivity, time-to-surgery, neoadjuvant treatment, and other health insurance. dGeneral complications: death, hemorrhage, blood transfusion, myocardial infarction (MI), stroke, urinary tract infection (UTI), pneumonia, deep vein thrombosis (DVT), pulmonary embolism (PE), other thrombosis, systemic inflammatory response syndrome (SIRS), severe sepsis, or septic shock. There were n = 0 deaths and n = 0 blood transfusions occurring during the 30-day follow-up. eBreast complications: surgical site infection (SSI), hematoma, seroma, lymphedema, or upper limb nerve injury. fSecond surgical procedure (lumpectomy or mastectomy) at least 7 days after the first surgery date and within 30 days of the index surgery. gInpatient encounter within 30 days after the initial surgery for any cause, excluding encounter related to reoperation. Bold text indicates statistical significance at the alpha=0.05 level.
The overall rate of reoperation within 30 days of the initial surgery was 16.3%. Women aged 40-49 had the highest rate (18.6%) and women aged 65+ had the lowest rate (13.5%) (Chi-square
In subsequent analysis stratified by surgery extent (partial or total and radical mastectomy), there were no statistically significant differences in the outcomes by age at diagnosis in models adjusted for potential confounders (see Appendix Table A3). However, the number of events was small (n < 11) among several age groups by surgery type which may affect estimate reliability and limit the ability to detect statistically meaningful differences.
Discussion
In the Military Health System, where women have insurance coverage and access to health services regardless of age, we noted some variation in short-term surgical outcomes by age at diagnosis among women with non-metastatic breast cancer who underwent surgery without immediate reconstruction. However, there were no overall statistically significant differences in 30-day postoperative outcomes by age group in the MHS population when adjusted for patient, tumor, and treatment factors. This is important as health systems strive to achieve optimal surgical outcomes for all patients regardless of clinical presentation of the disease.
Consistent with the epidemiology of breast cancer in the United States, younger women aged 18-39 or 40-49 had a higher frequency of diagnoses with pathologically unfavorable tumors (eg, regional stage, high grade, hormone receptor negative) relative to women aged 50-64 or ≥65 in the study population of DoW beneficiaries with breast cancer.4,6 This finding further highlights the need to understand how tumors among young women may differ biologically from tumors in older, postmenopausal women and how this may influence response to treatment. Notably, despite this more aggressive disease profile and higher rates of neoadjuvant therapy, younger women in the present study did not experience increased short-term complication rates, reinforcing the safety and feasibility of timely surgical management in this population. These findings are especially relevant for preserving access to adjuvant therapy and supporting return to duty among active-duty servicewomen.21,64 However, the current study did not include women receiving immediate reconstruction. Thus, the distribution of tumor characteristics and its implications for surgical management and outcomes may differ when these patients are otherwise included.
Our analysis found that general surgical complications were more common among older women (≥65) compared to other age groups, consistent with prior studies suggesting increased susceptibility to medical complications such as infections, thromboembolic events, or cardiovascular issues in older surgical patients.19,22 A population-based cohort study on breast cancer surgical outcomes found that medical complications were more common in women over 70 compared to those aged 50-69, while major surgical complications did not differ significantly by age group. 22 However, older women had a higher incidence of complications such as infections and cardiovascular issues following more extensive surgery (mastectomy). 22 In our study, after adjusting for comorbidities and other clinical factors, the association between age and general complications was no longer statistically significant. Breast-specific complications—including surgical site infection, hematoma, and lymphedema—occurred at similar rates across age groups, further supporting the idea that biological age alone may not be a sufficient indicator of risk for short-term postoperative morbidity in breast cancer surgery. These findings are supported by a study by Wolde et al. that found age was not a risk factor for developing post-operative complications after breast cancer surgery. 25 Type of surgery was the most important risk factor, as well as increased BMI. 25 Although women aged ≥65 had the highest comorbidity burden in our study, age was not independently associated with increased risk of complications after adjusting for comorbidity and other clinical variables. This reinforces the importance of assessing perioperative risk using individualized comorbidity measures rather than relying on age alone as a proxy for surgical risk.
One incidental finding was the increased risk of seroma among women aged 40-49 compared to those aged 50-64. Seroma formation is common after mastectomy, with some studies reporting rates over 50%.65,66 Surgical approach and technique, lymph node dissection, increased body weight, and tumor size may play a role in seroma development.65,66 However, seroma presence does not necessarily indicate a complication unless persistent or infected and many resolve without intervention. In our study, the overall frequency was low (<3%) relative to other studies and the absolute difference between age groups was small. We do not know from the data whether this represents an overall low occurrence or whether only those cases which required intervention were documented. Thus, the clinical relevance of the finding is unclear and may require further investigation into whether seromas are related to biological (eg, age) or clinical factors (eg, drain placement, surgical approach) in this population.
Rates of reoperation for cancer and hospital readmission did not differ significantly by age after multivariable adjustment, echoing findings from prior large-scale studies.49,50,58,59 The slightly higher unadjusted reoperation rate in women aged 40-49 and lower rate in women ≥65 in the present study is consistent with other national-level cohort data and may be explained by differences in tumor biology, margin status, and surgical approach rather than age alone as evidenced in the adjusted estimates.50,51 In a prior study of women in the MHS, Eaglehouse et al. found that age was not significantly related to rates of re-excision for women undergoing breast conserving surgery when other factors such as tumor location, size, and regional lymph node involvement were considered. 59 Similarly, the absence of age-related differences in hospital readmission in the current study supports the overall safety of breast cancer surgery across all adult age groups in a universally insured population. Collectively, these findings support a nuanced understanding of postoperative care needs across the age spectrum and suggest that short-term recovery is not necessarily compromised by younger age despite the more aggressive disease phenotype.
This study offers several strengths, including the use of a large, population-based cohort within the Military Health System, which ensures relatively uniform access to care and comprehensive capture of clinical data and thus reduces the possible effects of access to care on research results. However, certain limitations must be acknowledged. First, for any studies based on medical claims data, the use of administrative data to capture outcomes using ICD and CPT codes may under- or overestimate true event rates despite the use of validated definitions. Likewise, administrative data is subject to coding errors, although it is reviewed for completeness and accuracy to ensure proper billing and payment. However, such errors may not substantially differ by age, thus having minimal effect on our results. Second, the administrative data does not include clinical details which could be used to determine the severity of complications, whether intervention was needed to resolve a complication, or reason for reoperation (eg, obtain clean margins, drain placement, abscess removal). Thus, we cannot exclude possible differences by age in the severity of complications, and thus need for medical intervention, nor reoperations specific to achieving negative surgical margins vs management of a complication. The database also does not include clinical details of the surgery, such as type of anesthesia used, time in the operating room, surgeon specialty, etc. which may affect the outcome of surgery. Thus, we cannot account for any potential differences in these unmeasured confounders by age nor their impacts on the results. Third, the study period spanned from 2001 to 2014 which may not fully reflect changes in breast cancer surgery and perioperative management that have evolved over the past years, such as expansion of oncoplastic techniques and minimally invasive platforms and selective node surgery omission. While our analysis provides insights on potential differences in outcomes by age, the results should be interpreted in the context of standard surgical practice during the time period of the data (ie, 2001-2014) and the generalizability to women undergoing breast cancer surgery in the present may be limited. Also, HER2 status was mostly unavailable prior to 2010, as it was not a required item in cancer registries during this time. Thus, we were unable to fully account for differences in tumor biology (eg, triple negative breast cancer) by age and adjust for its possible effects in the regression models. Next, while the 30-day follow-up period captured immediate complications after surgery and is consistent with the ACS-NSQIP reporting window, it may not capture all complications related to surgery. Thus, we cannot exclude the possibility of any age-related differences in complications occurring beyond 30-days, nor the possibility of differences in complications after adjuvant therapy for these women undergoing breast cancer surgery. Finally, women eligible for care in the MHS may differ from those in the general population in underlying health conditions or behaviors and the study excluded women with immediate reconstruction. These factors may limit generalizability of the study results.
Conclusions
In the Military Health System, the overall risk of 30-day general and breast-specific complications, reoperations, and readmissions among younger and older women undergoing breast cancer surgery without immediate reconstruction did not differ significantly from middle-aged women with breast cancer after adjustment for clinical and demographic factors. The results in this universal health system suggest that age may play a limited role in short-term surgical outcomes for breast cancer. Surgical decision-making should continue to prioritize tumor characteristics, comorbidity burden, and other clinical factors rather than age alone when assessing perioperative risk. Nevertheless, future research is needed to evaluate whether there are differences in complication rates of cancer treatment over longer intervals (eg, months, years after surgery) by age and to assess for any differential impacts of complications on quality-of-life. Also, as surgical treatment of breast cancer continues to evolve, studies which consider breast reconstruction and different approaches to lymph node management and their use and outcomes by age will be needed.
Supplemental Material
Supplemental Material - Age at Breast Cancer Diagnosis and Short-Term Postoperative Outcomes for Women Treated in a Universal Health System
Supplemental Material for Age at Breast Cancer Diagnosis and Short-Term Postoperative Outcomes for Women Treated in a Universal Health System by Gabrielle Falco, Sarah Darmon, Matthew Nealeigh, Robert W. Krell, Craig D. Shriver, Kangmin Zhu, and Yvonne L. Eaglehouse in Cancer Control
Footnotes
Acknowledgement
The authors thank the Joint Pathology Center (JPC) for providing the Department of War (DoW) cancer registry data and the Defense Health Agency (DHA) for providing the Military Health System (MHS) data repository (MDR) data. The authors thank ICF International, the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF, Inc.), and the Uniformed Services University of the Health Sciences (USUHS) for data linkage and hosting.
Ethical Considerations
This retrospective cohort study used data from the Military Cancer Epidemiology (MilCanEpi) database. The MilCanEpi database was approved for access for research by the Uniformed Services University of the Health Sciences Institutional Review Board, Bethesda, Maryland (FWA 00001628) on 19 July 2019 (Reference #914142) and renewed on 4 March 2025 (Reference #981045).
Consent to Participate
The database study was reviewed by the Uniformed Services University of the Health Sciences Institutional Review Board (FWA 00001628; Reference #914142 and #981045) and it was determined that the requirement for informed consent was waived.
Funding
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Murtha Cancer Center Research Program (MCCRP) of the Department of Surgery, Uniformed Services University of the Health Sciences (USUHS) under the auspices of the Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF, Inc.), grant numbers HHU0001-16-2-0014 and HU0001-18-2-0032. The funding agency had no role in the study design; in the collection, analysis, and interpretation of data; or in the writing of the report.
Declaration of Conflicting Interests
The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: YE, SD, and KZ were employees of the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., a 501(c)(3) non-profit organization at the time the work was performed. The authors have no other potential conflicts of interest to declare.
Data Availability Statement
The data that support the findings of this study are not publicly available due to the restrictions in the access and use of the MilCanEpi data specified in the data sharing agreements and regulatory approvals. The Department of War cancer registry data and data dictionary may be requested from the Joint Pathology Center and online at https://jpc.capmed.mil/. The Military Health System Data Repository (MDR) data and data dictionary may be requested from the Defense Health Agency and online at
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Disclaimer
The contents of this abstract are the sole responsibility of the authors and do not necessarily reflect the views, assertions, opinions, or policies of the Uniformed Services University of the Health Sciences, the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., the Department of War, or the Departments of the Army, Navy, or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. government.
Supplemental Material
Supplemental material for this article is available online.
Appendix
References
Supplementary Material
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