Cardiac herniation post left upper lobectomy and thymectomy: a case report.

BACKGROUND: Cardiac herniation occurs when there is a residual pericardial defect post thoracic surgery and is recognised as a rare but fatal complication. It confers a high mortality and requires immediate surgical correction upon recognition. We present a case of cardiac herniation occurring post thymectomy and left upper lobectomy. CASE PRESENTATION: Initial presentation: A 48-year-old male, hypertensive smoker presented with progressive breathlessness and was found to have a left upper zone mass confirmed on CT biopsy as carcinoid of unclear origin. PET-CT revealed avidity in a left anterior mediastinal area, left upper lobe (LUL) lung mass, mediastinal lymph nodes, and a right thymic satellite nodule. Intraoperatively: Access via left thoracotomy and sternotomy. The LUL tumour involved the left thymic lobe (LTL), left superior pulmonary vein (LSPV), left phrenic nerve and intervening mediastinal fat and pericardium, which were resected en-masse. The satellite nodule in the right thymic lobe (RTL) was adjacent to the junction between the left innominate vein and superior vena cava (SVC). The pericardium was resected from the SVC to the left atrial appendage. Clinical deterioration: Initially the patient was doing well clinically on day 1, however there was sudden bradycardia, hypotension, clamminess, and oligoanuria, with raised central venous pressures and troponins. ECG: no capture in leads V1-2, but positive deflections seen on posterior leads. Echo: no acoustic windows, but good windows seen posteriorly. CXR: left mediastinal shift. Redo operation: After initial resuscitation and stabilisation on the intensive care unit, on day 2 a redo-sternotomy revealed cardiac herniation into the left thoracic cavity with the left ventricular apex pointing towards the spine, and inferior caval kinking. After reduction and repair of the pericardial defect with a fenestrated GoreTex patch, the patient recovered well with complete resolution of the ECG and CXR. CONCLUSION: Cardiac herniation can even occur following sub-pneumonectomy lung resections and should be considered as a differential when faced with a sudden clinical deterioration, warranting early surgical correction.

Rectal Hematoma Mimicking as a Gastrointestinal Stromal Tumor: An Atypical Endoscopic Ultrasound Finding.

Acute gastrointestinal bleeding (GIB) represents a frequently encountered condition that prompts individuals to seek urgent medical attention at the emergency department, often leading to subsequent hospitalization. GIB can range from self-limited bleeding to hemorrhagic shock. Multiple etiologies contribute to the occurrence of GIB. In this report, we present the case of an 84-year-old male with multiple medical comorbidities admitted with hemodynamically stable lower GIB. Colonoscopy demonstrated a submucosal mass without evidence of bleeding. He subsequently underwent an endoscopic ultrasound (EUS) with sonographic findings concerning for a gastrointestinal stromal tumor. However, pathological analysis from both colonoscopy and EUS indicated the presence of blood, but no evidence of malignancy. A follow-up EUS performed two months later showed a complete resolution of the previously observed submucosal mass, suggesting that the initial evaluation was likely a hematoma that has resolved completely.

Can Risk-Based Thromboprophylaxis Practice Guidelines be Safely Used in Esophagectomy Cases? Experience of an Academic Health System.

BACKGROUND: Venous thromboembolism (VTE) occurs in 3-11% of esophagectomy patients and is associated with increased mortality and morbidity. The use of validated VTE risk assessment tools and compliance with recommended practice guidelines remains unclear. In this study, we seek to determine the use of Caprini guideline indicated VTE prophylaxis and its effect on VTE and bleeding complications following esophagectomy. METHODS: Esophagectomy cases were identified from the Mayo Clinic electronic health records. Caprini score and VTE prophylaxis regimen received were determined retrospectively. VTE prophylaxis was identified as appropriate or inappropriate based on the Caprini score and prophylaxis received preoperative, during hospitalization, and after hospital discharge. Study cohorts were compared by Pearson Chi-square test, Fisher's Exact test, Kruskal-Wallis test, and logistic regression models. Stata/MP 16.1 was used for analysis. Odds ratios and 95% confidence intervals were reported for logistic regression models. A p-value < 0.05 was considered significant. RESULTS: Four hundred and fifty-six esophagectomy cases were analyzed. The median Caprini score was thirteen. Appropriate prophylaxis resulted in a 6.9-fold reduction in inpatient VTE. All 30- and 90-day post-discharge VTEs occurred in those not receiving Caprini guideline-indicated VTE prophylaxis. Inpatient, 30- and 90-day post-discharge bleeding rates were 7.68%, 0.91%, and 2.11%, respectively; however, bleeding was not increased with receipt of appropriate prophylaxis. CONCLUSION: In this esophagectomy cohort, Caprini guideline indicated VTE prophylaxis resulted in reduced inpatient VTE events without increasing bleeding complications. Risk-based VTE prevention measures should be considered in this patient cohort known to be at heightened risk for postoperative VTE.

Novel treatment of bronchopleural fistula in a lung transplant recipient with endobronchial sealant and endobronchial valve placement via robotic-assisted bronchoscopy.

Bronchopleural fistulas (BPFs) are a dreaded complication following pulmonary surgery. Endobronchial valves (EVs), with endobronchial sealant (ES), instilled with robotic bronchoscopy (RB), allow occlusion of BPF, avoiding surgery. The patient was a 71-year-old woman with a history of chronic obstructive pulmonary disease and bronchiectasis who underwent bilateral lung transplantation and wedge resection of the right middle lobe and left lingula. A BPF was discovered on postoperative day (POD) 21. Conservative measures with chest tubes failed, and robotic-assisted bronchoscopy aided in reaching the bronchial segment and instilling ES, and EV was deployed with the conventional bronchoscope. The pneumothorax was cleared 12 days later, and on POD 56, she was discharged. The RB procedure was successful, with no pneumothorax or BPF symptoms after a median follow-up of POD 284. Robotic endobronchial closure of BPF with EV and ES is an effective treatment option avoiding invasive surgeries.

Translating Policy to Practice: An Association Between Medicare Access and Children's Health Insurance Program Reauthorization Act Implementation and Palliative Care Consultations and Perioperative Mortality in Critical Care.

OBJECTIVES: To evaluate the 30-day postoperative mortality and palliative care consultations in patients that underwent surgical procedures in the United States before and after Medicare Access and Children's Health Insurance Program Reauthorization Act (MACRA) implementation. DESIGN: Retrospective, Observational cohort study. SETTING: Secondary data were collected from the U.S. National Inpatient Sample, the largest hospital database in the country. The time span was from 2011 to 2019. PATIENTS: Adult patients that electively underwent 1 of 19 major procedures. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was cumulative postoperative mortality in two study cohorts. The secondary outcome was palliative care use. We identified 4,900,451 patients and categorized them into two study cohorts: PreM: 2011-2014 ( n = 2,103,836) and PostM: 2016-2019 ( n = 2,796,615). Regression discontinuity estimates and multivariate analysis were used. Across all procedures, 149,372 patients (7.1%) and 156,610 patients (5%) died within 30 days of their index procedures in the PreM and PostM cohorts, respectively. There was no statistically significant increase in mortality rates around postoperative day (POD) 30 (POD 26-30 vs 31-35) for both cohorts. More patients had inpatient palliative consultations during POD 31-60 compared with POD 1-30 in PreM (8,533 of 2,081,207 patients [0.4%] vs 1,118 of 22,629 patients [4.9%]) and PostM (18,915 of 2,791,712 patients [0.7%] vs 417 of 4,903 patients [8.5%]). Patients were more likely to receive palliative care consultations during POD 31-60 compared with POD 1-30 in both the PreM (odds ratio [OR] 5.31; 95% CI, 2.22-8.68; p < 0.001) and the PostM (OR 7.84; 95% CI, 4.83-9.10; p < 0.001) cohorts. CONCLUSIONS: We did not observe an increase in postoperative mortality after POD 30 before or after MACRA implementation. However, palliative care use markedly increased after POD 30. These findings should be considered hypothesis-generating because of several confounders.

An Extremely Rare Case of Prostate and Bladder Wall Involvement of Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults and is characterized by monoclonal proliferation of B-cell lymphocytes which are morphologically mature, but immunologically dysfunctional. The primary sites of disease involvement include peripheral blood, lymph nodes, spleen, and bone marrow. CLL can also present locally and aggressively at extranodal sites. We describe the case of a 74-year-old gentleman with multiple medical comorbidities who was Foley catheter-dependent at baseline for bladder outlet obstruction. He was detected to have Rai stage I CLL following an inguinal lymph node biopsy and was on regular outpatient surveillance. Later, he underwent a prostate biopsy for evaluation of hematuria, results of which were consistent with CLL involvement in the prostate and urinary bladder. The patient was started on single-agent ibrutinib, and demonstrated an excellent clinical response to bladder outlet obstruction. His long-term Foley catheter was discontinued within 5 days of ibrutinib therapy. Unfortunately, 1 year later, he had disease progression, and therapy was changed to a single-agent rituximab, to which he is responding well. Our case is unique as it brings up the first reported case of prostate and bladder wall CLL.

Proton Therapy With Concurrent Chemotherapy for Thoracic Esophageal Cancer: Toxicity, Disease Control, and Survival Outcomes.

Purpose: When treating esophageal cancer with radiation therapy, it is critical to limit the dose to surrounding structures, such as the lung and/or heart, as much as possible. Proton radiation therapy allows a reduced radiation dose to both the heart and lungs, potentially reducing the risk of cardiopulmonary toxicity. Here, we report disease control, survival, and toxicity outcomes among patients with esophageal cancer treated with proton radiation therapy and concurrent chemotherapy (chemoradiation therapy; CRT) with or without surgery. Materials and Methods: We enrolled 17 patients with thoracic esophageal carcinoma on a prospective registry between 2010 and 2021. Patients received proton therapy to a median dose of 50.4-GyRBE (range, 50.4-64.8) in 1.8-Gy fractions.Acute and late toxicities were graded per the Common Terminology Criteria for Adverse Events, version 4.0 (US National Cancer Institute, Bethesda, Maryland). In addition, disease control, patterns of failure, and survival outcomes were collected. Results: Nine patients received preoperative CRT, and 8 received definitive CRT. Overall, 88% of patients had adenocarcinoma, and 12% had squamous cell carcinoma. With a median follow-up of 2.1 years (range, 0.5-9.4), the 3-year local progression-free, disease-free, and overall survival rates were 85%, 66%, and 55%, respectively. Two patients (1 with adenocarcinoma and 1 with squamous cell carcinoma) recurred at the primary site after refusing surgery after a complete clinical response to CRT. The most common acute nonhematologic and hematologic toxicities, respectively, were grades 1 to 3 esophagitis and grades 1 to 4 leukopenia, both affecting 82% of patients. No acute cardiopulmonary toxicities were observed in the absence of surgical resection. Reagarding surgical complications, 3 postoperative cardiopulmonary complications occurred as follows: 1 grade 1 pleural effusion, 1 grade 3 pleural effusion, and 1 grade 2 anastomotic leak. Two severe late CRT toxicities occurred: 1 grade 5 tracheoesophageal fistula and 1 grade 3 esophageal stenosis requiring a feeding tube. Conclusion: Proton radiation therapy is a safe, effective treatment for esophageal cancer with increasing evidence supporting its role in reducing cardiopulmonary toxicity.

Survival Outcomes of Lung Transplant Recipients From Donors With Abnormal Kidney Function.

BACKGROUND: Recovering lungs with pulmonary edema due to abnormal kidney function is considered one of the expanded selection criteria for lung transplant. The aim of this study is to assess lung transplant recipients' survival from donors with abnormal kidney function and to determine differences in lung recovery rates from donors with and donors without abnormal kidney function. METHODS: We reviewed the United Network for Organ Sharing registry for first-time adult lung transplant donors and recipients from June 2005 to March 2017. Donor kidney function was categorized into three groups based on estimated glomerular filtration rate: group I, greater than 60 mL/min; group II, 15 to 59 mL/min; and group III, less than 15 mL/min. Recipient survival was stratified based on estimated glomerular filtration rate using Kaplan-Meier. A multivariate Cox Regression model with known risk factors that affect survival was used to compare survival among groups. Comparison of lung recovery among the three groups was also performed. RESULTS: Lung recovery rates were 29.7% (15,670 of 52,747), 19.4% (3879 of 20,040), and 18.1% (704 of 3898) for groups I, II, and III, respectively. The 1-, 3-, and 5-year recipient survival rates were 86.2%, 69.2%, and 55.7% for group I; 84.9%, 66.9%, and 53.8% for group II; and 85.5%, 65.3%, and 50.3% for group III, respectively (adjusted P = .25; multivariate Cox regression method). When group I was used as reference, the adjusted hazard ratio for group II was 1.04 (95% CI, 0.98-1.10) and for group III, it was 1.08 (95% CI, 0.96-1.23), after adjusting with the multivariate Cox regression model. CONCLUSIONS: There was no significant difference in lung recipient survival. The lung recovery rate from donors with abnormal kidney function was lower compared with that of donors with normal kidney function.

Localization and surgical approach to mediastinal parathyroid glands.

BACKGROUND: Hyperactive parathyroid glands (PTGs) are in the mediastinum 4.3% of the time. Historically, localization and resection of these glands can be challenging. METHODS: We searched all operative notes involving a thoracic surgeon and a preoperative diagnosis of hyperparathyroidism from 2001 to 2019. RESULTS: Eighty-five cases were reviewed, of which 63 were included. Only 14 patients (22%) had de novo hyperparathyroid operations. Seventeen patients (27%) had single-photon emission computed tomography with computed tomography fusion (SPECT-CT) as the only preoperative localization test (excluding chest radiography and ultrasound), and all were resected successfully. The initial surgical approach was transcervical for 16 (27%) patients, however only 7 remained transcervical. 4 (6%) patients had an exploration in which the target lesion was resected but it was not parathyroid tissue. CONCLUSION: Most patients presenting with mediastinal PTG have had prior HPT surgery. The trend toward more focused HPT surgery may mean more de novo mediastinal PTG resections. An unambiguous functional and anatomic localization test, such as a spect-ct scan, is the best predictor of a successful resection. Ambiguous or discordant scans should be approached cautiously, and additional confirmatory tests are recommended. For suspected PTG located in the thymus, the thoracic surgeon should choose the most familiar approach to achieve complete thymectomy.

Safe heart flush technique during recovery from donors after circulatory death.

BACKGROUND: Donation after circulatory death is the donation after cardiac arrest. This technique has been employed and adopted by clinicians to overcome the shortage of available hearts for transplant. Warm ischemia time plays a pivotal role in the survival outcome of the heart recipients. AIM OF THE STUDY: To assess the efficacy of using the Foley catheter to flush the heart during procurement from donation after circulatory death donors. METHODS: We utilized a 2-WAY Foley catheter to flush the heart during procurement. The catheter was prepared and modified on the back table. RESULTS: We were successfully able to flush the heart within 3 minutes from skin incision with a good recipient outcome. CONCLUSIONS: Using the Foley catheter to flush the heart during recovery from donation after circulatory death donors was both efficient and fast.

Assessment of length of stay and cost of minimally invasive versus open thymectomies in patients with myasthenia gravis in Florida.

Background: Thymectomy has become a standard component in treatment for myasthenia gravis. The best surgical approach is still subject to debate. Minimally invasive surgery may have a lower mortality and morbidity rate, improved cosmetic results, and equivalent efficacy at improving neurologic symptoms to open approaches. We compared the perioperative outcomes and cost between the two techniques. Methods: We queried Florida Inpatient Discharge Dataset for patients who underwent thymectomy and had a primary diagnosis of non-thymomatous myasthenia gravis using International Classification of Diseases (ICD)-9 and ICD-10 codes to carry out this retrospective cohort study. The dates ranged between January 1st, 2013, to December 31st, 2018. We compared outcomes of patients who underwent minimally invasive thymectomy versus those who had open thymectomy. Results: An open approach was used in 108 patients, whereas a minimally invasive approach was used in 40 patients. Minimally invasive surgery group had a shorter length of stay (3.0 vs. 6.0 days, P<0.001) and had a non-significant lower total cost ($18.4K vs. $22.1K, P=0.186). After adjusting for age and Elixhauser score, length of stay for minimally invasive group was 32% (P=0.01) lower compared to the open surgery group. Conclusions: Patients who underwent minimally invasive thymectomy for Myasthenia gravis had a significantly shorter length of stay and a lower, although not significant, overall cost.

Chest wall resection for breast cancer: 21st century Mayo clinic experience.

BACKGROUND: We hypothesized full-thickness chest wall resection (FTCWR) with advanced surgical techniques and modern systemic therapy is safe, provides local control, and good overall survival. METHODS: Retrospective review of FTCWR (including rib or part of sternum) for breast cancer between 2000 and 2020. Primary endpoints included 90-day morbidities and all-cause mortality. Secondary endpoints were loco-regional and distant recurrence, DFS and overall survival (OS). RESULTS: A total of 35 patients met the criteria. 34 FTCWR were for recurrence and the median time to chest wall recurrence was 6 years. Tumor subtype was triple-negative in 51% and the remainder HR+ Her2-. 58% were palliative resections. FTCWR included rib(s) in 89% and portion of sternum in 57%; 94% required reconstruction and 80% were R0 resections. There were no 90-day mortalities. Overall morbidity was 10/35(28%). 17(49%) patients received neoadjuvant systemic therapy for their recurrence and three received neoadjuvant radiation. Adjuvant treatment included chemotherapy (8), endocrine therapy (3), and both (8). Ten patients (28%) received adjuvant radiation. The Median follow-up was 31 months and there were 6 (17%) loco-regional and 7 (20%) distant recurrences. OS was 86% and 67% at 1 and 3 years, respectively. CONCLUSION: FTCWR was associated with low morbidity, mortality, recurrence rates, and good OS. Selective FTCWR is safe and has acceptable short-term survival rates.

Pembrolizumab-Induced Acute Skin Reaction: A Case Report and Review of Literature.

The development of immune checkpoint inhibitors is considered to be one of the most important advances in cancer treatment. Pembrolizumab is an immune checkpoint inhibitor against programmed death-ligand 1 (PD-L1) receptor that has demonstrated antineoplastic activity against various malignancies including non-small cell lung cancer, melanoma, and triple-negative breast cancer. Pembrolizumab has been associated with significant dermatological adverse reactions, referred to as immune-related adverse events. The cutaneous adverse effects can affect the quality of life of the patient and can result in dose reduction or even discontinuation of the treatment. Hence it is of utmost importance to have a comprehensive understanding of the cutaneous toxicities for prompt initiation of treatment. We present the case of a 49-year-old male with metastatic non-small cell lung cancer (NSCLC) with 100% PD-L1 expression, who suffered a severe cutaneous reaction involving more than 95% of body surface area, following the first dose of pembrolizumab. He was treated with low-dose systemic steroids (prednisone 10 mg), to which he responded well. Since the patient showed excellent symptomatic and clinical response to pembrolizumab, it was not discontinued. The patient has not developed a rash with subsequent doses of pembrolizumab, and the steroids were tapered off.

Neoadjuvant Immune Checkpoint Inhibitors Plus Chemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma: Perioperative and Survival Outcomes.

Background: Immune checkpoint inhibitors (ICI) improve survival in patients with late-stage esophageal squamous cell carcinoma (ESCC) but have not been fully evaluated in locally advanced ESCC. Method: We retrospectively assessed outcomes of consecutive, treatment-naïve locally advanced ESCC (stage III or IVA) adults treated with neoadjuvant ICI plus chemotherapy followed by surgery, who refused or lacked access to radiotherapy, with regards to surgery feasibility, pathological response, and relapse-free survival (RFS). Results: We uneventfully treated 34 patients with the combined regimen in 2020. None reported grade III or higher toxic effects. All underwent surgery as planned: 32 received complete (R0) resections and 2 had microscopically positive margins (R1). Tumor downstaging occurred in 33 (97.1%) patients and 11 (32.4%) had pathologically complete response of the primary lesion. Median postoperative length of stay was 12 days (interquartile range: 11 to 17). All patients resumed a semi-liquid diet on discharge. The 90-day postoperative morbidity rate was 20.6% (7/34) with no mortalities. The 1-year RFS was 77.8% [95% CI, 64.2-94.2]. Conclusion: Neoadjuvant ICI plus chemotherapy was safe and resulted in significant downstaging, rendering inoperable tumors operable, relieving symptoms of dysphagia and prolonging survival for locally advanced ESCC patients who refused or lacked access to radiotherapy.

Combined cardiac surgery procedures and liver transplant: a single-center experience.

OBJECTIVE: Morbidity and mortality rates associated with liver transplant are high for patients with concomitant heart disease. Traditionally, such cases were considered contraindications for transplant. The objective of our study was to assess the outcome of combined surgical approaches. METHODS: A prospectively maintained database was analyzed of patients undergoing cardiac surgery and liver transplant at our institution. Twelve identified patients underwent combined cardiac operation and liver transplant. A control group was created (n = 24) with the same selection criteria. RESULTS: Median patient age was 64.94 years in the combined group vs 63.80 in the control, and in both groups, 58% were male. Left ventricular ejection fraction (0.60), body mass index (30.1), and median (range) score of the Model for End-stage Liver Disease (18 [9-33]) were the same in both groups. The cardiac operations combined with liver transplant were coronary artery bypass grafting, valve replacement procedures, and ascending thoracic aortic aneurysm repair. Piggyback liver transplant was performed for all patients. Survival periods of 1, 5, and 10 years for control vs combined cases were 90 vs 62%, 79 vs 55%, and 70 vs 45%, respectively (P = 0.03). CONCLUSION: Concomitant cardiac procedure and liver transplant is a valid treatment option and should be considered with risk stratification criteria of the patient with end-stage liver disease and cardiac surgical pathologic characteristics.

A 71-Year-Old Man With Diffuse Waxing and Waning Multifocal Lung Lesions, Empyema, and Episodic Fevers Reveals a Rare Diagnosis.

CASE PRESENTATION: A 71-year-old man with history of gastroesophageal reflux disease, chronic sinusitis, arthritis, hypothyroidism, and anemia of chronic disease initially sought treatment with a recurrent left pleural effusion along with other abnormal lung findings on chest CT scan. Before his referral, he was being managed for 3 years at his local hospital for waxing and waning fevers, fatigue, productive cough, chills, and night sweats. He did not report any hemoptysis or chest pain, but reported weight loss of 13 kgs in 15 months. During those 3 years, he was treated with multiple courses of antibiotics and steroids with temporary relief of symptoms. At that time, his chronic sinusitis was suspected to be the cause of his symptoms and he underwent balloon sinuplasty. He was receiving daily sublingual immunotherapy for inhaled respiratory allergens for the previous year after showing positive test results for 17 inhaled allergens. The patient had no other known immunologic workup before our evaluation.

An Extremely Rare Case of Metastatic Merkel Carcinoma of the Liver.

Merkel cell carcinoma (MCC) is a rare but highly aggressive skin cancer with neuroendocrine features. The important risk factors in the development of MCC include immunocompromised state, advanced age, and White skin complexion. The pathogenesis is associated with either the presence of Merkel cell polyomavirus or chronic exposure to ultraviolet radiation. MCC usually occurs in the sun-exposed areas of the skin and has the potential for regional and distant metastasis. Only 8% of the cases of MCC present with distant metastatic disease with liver, lungs, bone, and brain being commonly involved. Here, we report such an extremely rare case of a 78-year-old gentleman with a history of cutaneous T-cell lymphoma, who presented to the hospital with abnormally elevated liver enzymes, which on further evaluation was detected to have metastatic MCC of the liver.

The Black Esophagus.

Acute esophageal necrosis (AEN), commonly referred to as black esophagus, is a rare clinical condition resulting from a combination of ischemic insult and thromboembolic injury to the esophagus. It is characterized by the circumferential black appearance of the esophagus. The risk factors for the development of AEN include coronary artery disease (CAD), diabetes mellitus, hypertension, malignancy, and alcohol use disorder. The treatment is directed at correcting the underlying medical conditions, supportive measures, and gastric acid suppression. We present the case of a 60-year-old female with multiple medical comorbidities who was detected to have a black esophagus during the evaluation of anemia.

Adrenal-permissive HSD3B1 genetic inheritance and risk of estrogen-driven postmenopausal breast cancer.

BACKGROUNDGenetics of estrogen synthesis and breast cancer risk has been elusive. The 1245A→C missense-encoding polymorphism in HSD3B1, which is common in White populations, is functionally adrenal permissive and increases synthesis of the aromatase substrate androstenedione. We hypothesized that homozygous inheritance of the adrenal-permissive HSD3B1(1245C) is associated with postmenopausal estrogen receptor-positive (ER-positive) breast cancer.METHODSA prospective study of postmenopausal ER-driven breast cancer was done for determination of HSD3B1 and circulating steroids. Validation was performed in 2 other cohorts. Adrenal-permissive genotype frequency was compared between postmenopausal ER-positive breast cancer, the general population, and postmenopausal ER-negative breast cancer.RESULTSProspective and validation studies had 157 and 538 patients, respectively, for the primary analysis of genotype frequency by ER status in White female breast cancer patients who were postmenopausal at diagnosis. The adrenal-permissive genotype frequency in postmenopausal White women with estrogen-driven breast cancer in the prospective cohort was 17.5% (21/120) compared with 5.4% (2/37) for ER-negative breast cancer (P = 0.108) and 9.6% (429/4451) in the general population (P = 0.0077). Adrenal-permissive genotype frequency for estrogen-driven postmenopausal breast cancer was validated using Cambridge and The Cancer Genome Atlas data sets: 14.4% (56/389) compared with 6.0% (9/149) for ER-negative breast cancer (P = 0.007) and the general population (P = 0.005). Circulating androstenedione concentration was higher with the adrenal-permissive genotype (P = 0.03).CONCLUSIONAdrenal-permissive genotype is associated with estrogen-driven postmenopausal breast cancer. These findings link genetic inheritance of endogenous estrogen exposure to estrogen-driven breast cancer.FUNDINGNational Cancer Institute, NIH (R01CA236780, R01CA172382, and P30-CA008748); and Prostate Cancer Foundation Challenge Award.