Mutter, Robert W.

Abstract Background: Sarcopenia, characterized by the loss of muscle mass, has emerged as a negative prognostic factor in cancer patients. It has been associated with poorer outcomes and increased treatment-related morbidity. Post-mastectomy breast radiation therapy (RT) increases the likelihood of reconstructive complication, with up to 20% of reconstructed women requiring implant removal. The factors that lead to these complications are poorly understood and likely multifaceted. We investigated the relationship between pre-radiation therapy sarcopenia and post-mastectomy reconstruction outcomes. Methods: Chart review was performed to determine demographic, medical, and treatment variables, including reconstruction complication events and failures in breasts treated with mastectomy, immediate reconstruction, and RT. Reconstruction failure was defined as tissue expander or implant removal, resulting in no final reconstruction or autologous reconstruction only. Reconstruction complications included surgical site infection, late infection (1 year post-RT), seroma development, flap necrosis, nipple necrosis, wound dehiscence, capsular contracture, hematoma, extrusion, leak, venous congestion, and unplanned reoperation. An axial slice at the L2 or L3 vertebral body from the radiation therapy planning CT scan was analyzed for skeletal muscle area using a previously validated algorithm, with manual review and adjustment as indicated. Sarcopenia was defined by skeletal muscle index (SMI, skeletal muscle area in cm2 divided by patient’s height squared) below 34.4 cm2/m2. Chi-square, Kaplan Meier, and univariate Cox regression tests were used for analysis. Results: Ninety-nine women with breast cancer who underwent mastectomy, reconstruction, and RT were included in this study. All women had immediate reconstruction: 93 women had tissue expander placement while six women had permanent implant placement. Mean age was 47.5 years (SD 10.6) at diagnosis and median BMI was 24.8. Seventy-six percent were non-smokers, 24% were former smokers, and only 16 (16.2%) and 3 (3.0%) had hypertension or diabetes, respectively. Median follow-up was 2.7 years. Median SMI was 38 cm2/m2 and 18 (18%) met criteria for sarcopenia (SMI < 34.4 cm2/m2). Mastectomy was bilateral in 79 women, skin-sparing in 61, and nipple sparing in 31. Bilateral mastectomy was less frequent amongst women with sarcopenia (61%) compared to 84% of those without sarcopenia (p=0.03). After RT, twenty-three women required unplanned reoperation. Within these 23 women, there were 45 total complications. Complications included surgical site infection (n=18), capsular contracture (n=12), seroma (n=4), wound dehiscence (n=3), and others (n=8). However, only 8 women had reconstructive failure and none were sarcopenic at the time of the RT planning scan. Any complication or failure after RT occurred in similar proportions of patients with and without sarcopenia: 38% and 30%, respectively. Kaplan-Meier curves and univariate Cox regression models showed no significant difference in time to failure (p = 0.380) or time to any event (complication or failure) (p=0.53), between sarcopenic and non-sarcopenic patients. Conclusion: Sarcopenia, using SMI < 34.4 cm2/m2 on pre-radiotherapy planning scans, was not associated with an increased risk of post-radiotherapy reconstructive complication or failure in this selected cohort of non-smokers. Few women had sarcopenia at the time of operation, and results should be validated in a larger series. Citation Format: Yasamin Sharifzadeh, Robert Gao, William S. Harmsen, Jason Klug, Panagiotis Korfiatis, Kimberly Gergelis, Dean A. Shumway, Robert Mutter, Kimberly Corbin. Sarcopenia and Post-Mastectomy Breast Reconstruction Outcomes after Radiation Therapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-52.

Abstract Objective Patients with hormone receptor positive (HR+), HER2- metastatic breast cancer frequently require radiation therapy (RT) in addition to systemic therapy for disease control and symptom management. CDK 4/6 inhibitors are increasingly used in the care of hormone positive breast cancers. Stereotactic body radiotherapy (SBRT), a form of very focused high dose radiation, is also increasingly used in the care of metastatic breast cancer. Limited data have reported on the safety of palliative RT with CDK4/6 inhibitors, with some reports demonstrating synergistic effects with potential for increased toxicity. The objective of our study is to assess toxicity among patients who received SBRT, stereotactic radiosurgery (SRS), or other high dose RT along with CDK 4/6 inhibitors for treatment of metastatic breast cancer. Methods Women with metastatic breast cancer who received SBRT, SRS, or other higher dose RT with CDK 4/6 inhibitors at any point in their treatment between 2013 and 2021 were retrospectively identified. Timing of radiation therapy, either before, during, or after CDK 4/6 inhibitor use was assessed, as well as the interval between the two treatments. Treatment sites for radiotherapy included lung/chest, spine, and brain metastases. Physician assessed adverse events were obtained through clinical follow up and graded using CTCAE v5. Local control and OS were reported. Results Twenty patients met study inclusion criteria. Patients received radiation therapy and CDK 4/6 inhibitors concurrently (within 7 days) [n=7, 35%], within 30 days (RT pre-CDK 4/6 inhibitor use) [n=3, 15%], and greater than 30 days (RT pre-CDK 4/6 inhibitor use [n=6, 30%] and RT post-CDK 4/6 inhibitor use [n=4, 20%]). Radiation treatment sites were spine [n=10, 55%], brain [n=6, 30%], and lung/chest wall [n=3, 15%]. Radiation doses were as follows: 60 Gy in 5 fractions [n=1, 5%], 50 Gy in 5 fractions [n=2, 10%], 55 Gy in 20 fractions (chest wall recurrence) [n=1, 5%], 35 Gy in 15 fractions [n=1, 5%], 30 Gy in 10 fractions [n=6, 30%], 30 Gy in 3 fractions [n= 4, 20%], 24 Gy in 1 fraction [n=3, 15%], 20 Gy in 5 fractions [n=2, 10%]. Palbociclib was used in 85% of patients [n=17] and abemaciclib in 15% [n=3]. Median follow up for surviving patients was 4.7 years [IQR: 2.5-6.8 years]. Local control was achieved in 85% of patients [n=17]. Median OS was 2.7 years [IQR: 0.1-6.8 years]. Grade 2 toxicity [n=9, 45%] and grade 3 toxicity [n=3, 15%] was reported across all three treatment areas, with grade 2 or 3 fatigue [n=7, 35%] being the most frequently reported toxicity. In the spine treatment group, 1 patient who had CDK 4/6 inhibitor use within 30 days of radiotherapy experienced a grade 3 vertebral compression fracture as well as grade 3 fatigue. In the lung/chest wall treatment group, the patient treated to 55 Gy in 20 fractions to the chest wall with concurrent use had grade 3 skin/wound toxicity requiring prolonged wound care before healing. In the intra-cranial SRS group, grade 3 fatigue was reported in 1 patient with concurrent use. Conclusion The use of CDK 4/6 inhibitors concurrently with or within 30 days of radiation therapy was generally well tolerated with limited grade 3 toxicity. Two of three reports of grade 3 toxicity occurred with concurrent treatment. Due to the potential radiosensitizing properties of CDK 4/6 inhibitors, it may be prudent to hold combined treatment when clinically feasible. Further study is needed to validate these results. Citation Format: Kiran Chauhan, Roman O. Kowalchuk, Allison E. Garda, Dean A. Shumway, Mark R. Waddle, Robert Mutter, Kimberly Corbin. Safety of stereotactic body radiation therapy, stereotactic radiosurgery, and other radiation therapy with use of CDK 4/6 inhibitors for hormone receptor positive (HR+), HER2- metastatic breast cancer: a retrospective cohort study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-05.

Abstract Purpose/Objectives: Proton therapy is under investigation in breast cancer as a strategy to reduce heart and lung exposure, which is associated with late cardiopulmonary adverse events and secondary malignancy. To date, studies investigating postmastectomy radiotherapy (PMRT) with protons have used conventional fractionation. We hypothesized that condensing treatment to 15 fractions would be safe based on evidence that breast cancer is more sensitive to higher dose fractions than surrounding normal tissues. Materials/Methods: We conducted a randomized non-inferiority phase II trial comparing conventional and hypofractionated proton PMRT with primary endpoint of 24-month complication rate (defined as grade 3 or higher late adverse events using CTCAE, v 4.0 and/or unplanned surgical intervention in patients undergoing mastectomy with reconstruction). With a 10% non-inferiority margin the study ensured 80% power and had a one sided-type I error rate of 0.05. Cardiotoxicity was assessed with serial transthoracic conventional and 2-dimensional speckle tracking echocardiography (2D-STE). Eligibility included age ≥ 18 years with non-inflammatory breast cancer resected by mastectomy with indications for PMRT. Assignment of treatments was balanced with respect to immediate breast reconstruction (IBR). Conventional fractionation group received 50 Gy in 25 fractions of 2 Gy, and hypofractionation group received 40.05 Gy in 15 fractions of 2.67 Gy (RBE 1.1). Target volume included the chest wall and axillary, supraclavicular, and internal mammary lymph nodes. All patients were treated with multi-field optimized pencil beam scanning (intensity modulated proton therapy). Results: Between 2016 and 2018, 82 patients were enrolled and randomized (41 conventional, 41 hypofractionation). Median patient age was 52 years. 32.9% were staged T3-T4 and 79.3% node positive at diagnosis. 57 of 82 patients (69.5%) elected IBR. The median mean heart dose was 0.49 Gy and the median ipsilateral lung volume receiving 40% of prescription or greater (V40%) was 13.6%. No significant changes on conventional or 2D-STE at end-of-treatment or 3-month follow-up compared to baseline were observed. The rate of ≥ grade 2 acute dermatitis was lower with hypofractionation (44% vs 15%, p = 0.006). Other ≥ grade 2 acute adverse events including esophagitis (0 vs 5%), infection (5% vs 2.4%) and skin hyperpigmentation (7.3% vs 4.8%) were not significantly different between the two arms. With a median follow-up of 38.3 months, the 24-month complication rate was conventional 14.6% vs hypofractionation 17.1% (absolute difference 2.4%, p=0.17, 95% CI [-, 15.7%]). In patients with IBR, 6 of 28 (21.4%) conventional and 7 of 29 (24.1%) hypofractionated patients developed complications (p =0.80). There was no significant difference in 3-year disease-free survival between the conventional (89.4%; 95% CI 80.0 – 99.8%) and hypofractionated (92.4%, 95% CI 84.5 – 100.0%) arms (p = 0.91). One local recurrence occurred in the hypofractionated arm simultaneous with regional and distant relapse. The remaining 6 recurrences were isolated distant events. Conclusions: Proton PMRT provided excellent locoregional control and normal tissue sparing. There were no subclinical echocardiographic changes indicative of radiation-induced cardiac dysfunction. Hypofractionation resulted in comparable disease control, tolerability and reconstruction outcomes as conventional fractionation. Although non-inferiority of hypofractionation could not be established based on the upper bound of the 95% confidence interval for complication rate being greater than 10%, both conventional and hypofractionation may be considered appropriate regimens for ongoing phase 3 randomized trials comparing photon and proton radiotherapy. Citation Format: Robert Mutter, Sharmila Giri, Briant Fruth, Nicholas Remmes, Aman Anand, Kathryn Ruddy, Hector Villarraga, Sebastian Santos Patarroyo, Elizabeth Yan, Kenneth Merrell, Lisa McGee, Tamara Vern-Gross, Bradley Stish, Robert Gao, Judy C. Boughey, Sean Park, Kimberly Corbin, Carlos Vargas. Phase II randomized trial of conventional versus hypofractionated post-mastectomy proton radiotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS4-05.

Abstract Background: Partial breast irradiation (PBI) is an established option for selected patients with early stage breast cancer. The optimal technique, target volume and dose/fractionation for PBI has yet to be defined. The most studied regimen in North America (38.5 Gy in 10 fractions twice daily) has been associated with cosmetic deterioration. We hypothesized that condensing treatment and reducing the total administered dose could improve the therapeutic ratio in luminal breast cancer and DCIS based on emerging evidence that breast cancer is more sensitive than surrounding normal tissues to high dose fractions. Herein, we report cosmetic, tolerability, disease control, and patient reported outcomes of a novel ultra-accelerated PBI regimen. Methods: We conducted a single arm, three cohort trial of photon, proton, and brachytherapy PBI. Technique was selected at physician and patient discretion. Eligible women were age ≥ 50 years with estrogen receptor positive (ER+), sentinel lymph node negative invasive or in-situ breast cancer measuring ≤ 2.5 cm. The regimen was designed to have comparable biologically equivalent effect as 40 Gy in 15 fractions, assuming an α/β ratio of 3.5. Intracavitary brachytherapy target volume was lumpectomy cavity plus 1 cm and prescribed 21 Gy in 3 fractions. Photon and proton target volumes were post-operative tumor bed plus 1 cm and a 3 mm setup uncertainty margin, prescribed 21.9 Gy (RBE) in 3 fractions, and delivered with image guidance. The primary outcome was the percentage difference in patients with adverse cosmesis (defined as fair or poor cosmesis) at 3 years compared to baseline pre-PBI, as assessed by trained nurses using the 4-point Harvard breast cosmesis scale. Patients also completed quality of life surveys and self-reported cosmesis using the 4-point scale. Locoregional and distant recurrence-free survival was determined using the Kaplan-Meier method. Adverse events were assessed using CTCAE, v 4.0. Results: Between 2015 and 2017, 163 patients were treated: photons in 58, protons in 48, and brachytherapy in 57. Median patient age was 66 years. 129 (79%) patients had invasive breast cancer (all ER+) and 34 (21%) had DCIS (83% ER+). Median tumor size was 1.1 cm. Grade was 2-3 in 102 (63%). The median mean heart/ipsilateral lung doses were photons 0.1/1.6 Gy, protons <0.001/0.1 Gy, and brachytherapy 0.5/0.9 Gy. Median follow-up was 4.1 years (IQR 3.9-5.0). The proportion of patients with adverse cosmesis (by RN assessment) was 14.3% at baseline and 3.8% at 3 years, with four patients (1 photon, 1 proton, 2 brachytherapy) experiencing cosmetic deterioration at 3 years from baseline. The proportion with adverse cosmesis by self-report at 3 years was 2.4%, with three patients (1 photon, 1 proton, 1 brachytherapy) reporting cosmetic deterioration. Four patients developed locoregional recurrence (1 photons, 2 protons, 1 brachytherapy); three were local only and one was local and distant. 4-year locoregional recurrence and distant metastasis-free survival were 97.9% and 97.4%, respectively. There were 2 treatment related ≥ grade 2 late events (grade 2 fibrosis and grade 2 seroma, both brachytherapy associated), and no evidence of deterioration in patient-reported pain, fatigue, breast related or overall quality of life, as assessed by the patient reported outcomes version of the CTCAE, 10-point linear analog scales, and the breast cancer treatment outcomes scale. Conclusions: Ultra-accelerated 3-fraction PBI exquisitely spared normal tissues and was associated with favorable cosmetic outcomes, disease control, and excellent long-term tolerability. This ‘precision-radiotherapy’ approach may optimize the therapeutic ratio over more aggressive radiotherapy options as well as radiotherapy omission, particularly in patients with long life expectancies. Citation Format: Robert Mutter, Tina Hieken, Todd DeWees, Arslan Afzal, Stephanie Kenison, Laura Vallow, Christopher Deufel, Nicholas Remmes, Kathryn Ruddy, Judy Boughey, Keith Furutani, Amy Degnim, James Jakub, Tamara Vern-Gross, Dean Shumway, William Wong, Samir Patel, Lisa McGee, Minetta Liu, Carlos Vargas, Daniel Visscher, Bradley Stish, Deanna Pafundi, Mark Waddle, Michael Golafshar, Michele Halyard, Kimberly Corbin, Sean Park. Ultra-accelerated photon, proton, and brachytherapy partial breast irradiation: Primary results of the Mayo 3-fraction trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD7-03.

Abstract Proton Bragg peak irradiation has a higher ionizing density than conventional photon irradiation or the entrance of the proton beam profile. Whether targeting the DNA damage response (DDR) could enhance vulnerability to the distinct pattern of damage induced by proton Bragg peak irradiation is currently unknown. Here, we performed genetic or pharmacologic manipulation of key DDR elements and evaluated DNA damage signaling, DNA repair, and tumor control in cell lines and xenografts treated with the same physical dose across a radiotherapy linear energy transfer spectrum. Radiotherapy consisted of 6 MV photons and the entrance beam or Bragg peak of a 76.8 MeV spot scanning proton beam. More complex DNA double-strand breaks (DSB) induced by Bragg peak proton irradiation preferentially underwent resection and engaged homologous recombination (HR) machinery. Unexpectedly, the ataxia-telangiectasia mutated (ATM) inhibitor, AZD0156, but not an inhibitor of ATM and Rad3-related, rendered cells hypersensitive to more densely ionizing proton Bragg peak irradiation. ATM inhibition blocked resection and shunted more DSBs to processing by toxic ligation through nonhomologous end-joining, whereas loss of DNA ligation via XRCC4 or Lig4 knockdown rescued resection and abolished the enhanced Bragg peak cell killing. Proton Bragg peak monotherapy selectively sensitized cell lines and tumor xenografts with inherent HR defects, and the repair defect induced by ATM inhibitor coadministration showed enhanced efficacy in HR-proficient models. In summary, inherent defects in HR or administration of an ATM inhibitor in HR-proficient tumors selectively enhances the relative biological effectiveness of proton Bragg peak irradiation. Significance: Coadministration of an ATM inhibitor rewires DNA repair machinery to render cancer cells uniquely hypersensitive to DNA damage induced by the proton Bragg peak, which is characterized by higher density ionization. See related commentary by Nickoloff, p. 3156

Abstract Background: The clinical utility of routine annual mammogram after curative-intent treatment for male breast cancer is uncertain. There is potentially greater value after lumpectomy (as surveillance for ipsilateral recurrence) than mastectomy (as screening for a new contralateral cancer). The goal of this study was to assess real world use of mammography in men during the first year after lumpectomy or mastectomy to treat breast cancer. Methods: Administrative claims data from OptumLabs Data Warehouse (a large US database that includes privately insured patients and Medicare Advantage-insured enrollees from all 50 states and of all ages and ethnic and racial groups) were used to identify men treated with breast surgery for a new diagnosis of breast cancer between 2007 and 2017. We required continuous coverage starting at least 6 months prior to the non-metastatic breast cancer diagnosis and continuing until at least 13 months after the breast surgery. Our primary endpoint was the proportion of patients who had at least one mammogram during the year (13-month period, to allow for scheduling and other logistical delays) after lumpectomy or mastectomy. Univariate and multivariate testing were performed to identify predictors of mammography (with p<0.05 used as the threshold for statistical significance for both). Our secondary endpoint was the proportion with at least one mammogram within 24 months of surgery, performed in a subset who maintained their insurance coverage for at least that duration. Results: The 13-month analysis included 730 men with a median age at diagnosis of 62 years (Range: 25 to 87 years) and a median follow-up duration of 35 months (Range: 13 to 134 months). 209 (29%) of these men underwent mammography within 13 months after surgery. The characteristics of patients who underwent mammography and those who did not are shown in Table 1. Mammography was more likely after lumpectomy than mastectomy (41% vs. 27%) and after radiation therapy (41% vs. 32% in those who did not receive radiation). In a multivariate logistic regression model, more recent diagnosis (2015+) was associated with lower odds of undergoing mammography, while receipt of radiation was associated with higher odds of undergoing mammography. In the subset of patients with two or more years of post-surgery coverage (n=527), the proportion who had at least one mammogram during that 24-month period was 49% after lumpectomy and 40% after mastectomy. Conclusions: In this insured cohort, 73% of men did not undergo mammography within a year after mastectomy, and 59% did not within a year after lumpectomy. Mammography was less likely in patients diagnosed more recently (perhaps due to acknowledgment of the unique aspects of male breast cancer including a relatively low risk of contralateral second primary tumors), and more likely in those who received radiation. These variations in practice likely result from the paucity of evidence-based guidelines for male breast cancer survivorship care. More research is needed pertaining to whether or not mammograms improve clinical outcomes after curative intent treatment for male breast cancer. Table 1: Patient characteristics associated with receipt of mammogram within first 13 months after male breast cancer surgeryUnivariate AnalysisMultivariate AnalysisNo Mammogram (N=521)Mammogram (N=209)P-value, chi-square testOdds Ratio (OR) and 95% CIP-value for ORAge Group:0.1225-4966 (12.7%)32 (15.3%)Reference50-64216 (41.5%)98 (46.9%)0.99 (0.60, 1.63)0.9665-74112 (21.5%)44 (21.1%)0.87 (0.48, 1.57)0.6575+127 (24.4%)35 (16.7%)0.57 (0.30, 1.07)0.08Census Region:0.52Midwest138 (26.5%)59 (28.2%)ReferenceNortheast97 (18.6%)47 (22.5%)1.10 (0.68, 1.78)0.69South223 (42.8%)79 (37.8%)0.74 (0.49, 1.11)0.15West63 (12.1%)24 (11.5%)0.83 (0.47, 1.47)0.51Year of diagnosis:0.072007-2010126 (24.2%)65 (31.1%)Reference2011-2014199 (38.2%)82 (39.2%)0.80 (0.54, 1.20)0.292015+196 (37.6%)62 (29.7%)0.63 (0.41, 0.96)0.03Elixhauser Category:0.250148 (28.4%)69 (33.0%)Reference1-2218 (41.8%)74 (35.4%)0.85 (0.56, 1.28)0.433+155 (29.8%)66 (31.6%)1.18 (0.75, 1.87)0.47Surgery Type:0.005Lumpectomy55 (10.6%)38 (18.2%)ReferenceMastectomy466 (89.4%)171 (81.8%)1.57 (0.97, 2.55)0.07Chemotherapy:0.79No301 (57.8%)123 (58.9%)ReferenceYes220 (42.2%)86 (41.1%)0.79 (0.54, 1.16)0.23Radiation:0.02No355 (68.1%)124 (59.3%)ReferenceYes166 (31.9%)85 (40.7%)1.51 (1.03, 2.20)0.03 Citation Format: Siddhartha Yadav, Lindsey Sangaralingham, Stephanie R. Payne, Karthik V. Giridhar, Tina J. Hieken, Judy C. Boughey, Robert W. Mutter, John R. Hawse, Rafael E. Jimenez, Rachel A. Freedman, Sadia Choudhery, Fergus J. Couch, Celine M. Vachon, Nilay Shah, Roberto A. Leon-Ferre, Kathryn J. Ruddy. Surveillance mammography after treatment for male breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-17-08.

Background Male breast cancer (MBC) is a rare disease for which there is limited understanding of treatment patterns and prognostic factors. Methods Men with TNM stage I to stage III breast cancer diagnosed between 2004 and 2014 in the National Cancer Data Base were included. Trends in treatment modalities were described using the average annual percentage change (AAPC) and estimated using Joinpoint software for the analysis of trends. Kaplan‐Meier curves and the multivariate Cox proportional hazards regression model were used to compare survival between subgroups and to identify prognostic factors. Results A total of 10,873 MBC cases were included, with a median age at diagnosis of 64 years. Breast‐conserving surgery was performed in 24% of patients, and 70% of patients undergoing breast conservation received radiotherapy. Approximately 44% of patients received chemotherapy, and 62% of patients with estrogen receptor–positive disease received endocrine therapy. Oncotype DX was ordered in 35% of patients with lymph node–negative, estrogen receptor–positive/human epidermal growth factor receptor 2 (HER2)‐negative tumors. During the study period, there was a significant increase in the rates of total mastectomy, contralateral prophylactic mastectomy, radiotherapy after breast conservation, ordering of Oncotype DX, and the use of endocrine therapy ( P < .05). On multivariate analysis, factors found to be associated with worse overall survival were older age, black race, higher Charlson Comorbidity Index, high tumor grade and stage of disease, and undergoing total mastectomy. Residing in a higher income area; having progesterone receptor–positive tumors; and receipt of chemotherapy, radiotherapy, and endocrine therapy were associated with better overall survival. Conclusions Despite the lack of prospective randomized trials in patients with MBC, the results of the current study demonstrated that the treatment of this disease has evolved over the years. These findings further the understanding of the modern treatment and prognosis of MBC, and identify several areas for further research.