Association of progesterone receptor status with 21-gene recurrence score and survival among patients with estrogen receptor-positive breast cancer.

BACKGROUND: Progesterone receptor (PR)-negative tumors have been shown to have worse prognosis and were underrepresented in recent trials on patients with estrogen receptor (ER)-positive breast cancer. The role of PR-negative status in the context of 21-gene recurrence score (RS) and nodal staging remains unclear. METHODS: The National Cancer Database (NCDB) was queried for women diagnosed between 2010 and 2017 with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative, pT1-3N0-1a breast cancer. Logistic and Cox multivariable analyses (MVA) were performed to identify association of PR status with high RS (> 25) and overall survival (OS), respectively. RESULTS: Among 143,828 women, 130,349 (90.6%) and 13,479 (9.4%) patients had PR-positive and PR-negative tumors, respectively. Logistic MVA showed that PR-negative status was associated with higher RS (> 25: aOR 16.15, 95% CI 15.23-17.13). Cox MVA showed that PR-negative status was associated with worse OS (adjusted hazards ratio [aHR] 1.20, 95% CI 1.10-1.31). There was an interaction with nodal staging and chemotherapy (p = 0.049). Subgroup analyses using Cox MVA showed the magnitude of the chemotherapy benefit was greater among those with pN1a, PR-negative tumors than pN1a, PR-positive tumors (PR-positive: aHR 0.57, 95% CI 0.47-0.67; PR-negative: aHR 0.31, 95% CI 0.20-0.47). It was comparable among those with pN0 tumors regardless of PR status (PR-positive: aHR 0.74, 95% CI 0.66-0.82; PR-negative: aHR 0.63, 95% CI 0.51-0.77). CONCLUSION: PR-negative tumors were independently correlated with higher RS and were associated with greater OS benefits from chemotherapy for pN1a tumors, but not pN0 tumors.

Survival outcome of adjuvant chemotherapy and high 21-gene recurrence score in early-stage breast cancer.

Among patients with early-stage breast cancer and a high 21-gene recurrence score (RS) ≥ 26, it remains unclear on whether those with RS 26-30 would benefit from chemotherapy with a comparable magnitude as those with RS > 30. In addition, RS > 30 as an independent prognostic factor for breast cancer-specific survival (BCSS) and overall survival (OS) compared to RS 26-30 also remains unclear. The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients diagnosed between 2010 and 2013 with hormone receptor-positive, HER2-negative, and T1-2N0 breast cancer with a RS ≥ 26. Primary end points were OS and BCSS, evaluated by using Kaplan-Meier method, log-rank test, and Cox multivariable analysis. Subgroups of RS 26-30 and RS > 30 were examined using propensity score matching to address selection bias. Among 5054 patients who met the inclusion criteria, adjuvant chemotherapy was associated with improved OS (HR 0.66, 95% CI 0.53-0.83, P < .001) and BCSS (HR 0.61, 95% CI 0.45-0.83, P = .001). In the subgroup of 943 matched pairs of patients with RS 26-30, the addition of chemotherapy remained statistically significant (OS: HR 0.52, 95% CI 0.34-0.79, P = .003; BCSS: HR 0.42, 95% CI 0.22-0.81, P = .009). Among 1194 matched pairs who underwent adjuvant chemotherapy, those with RS > 30 had worse outcomes than others with RS 26-30 (OS: HR 1.68, 95% CI 1.17-2.42, P = .005; BCSS: HR 1.92, 95% CI 1.17-3.15, P = .01). Our study builds on prior literature using a population-based database to suggest the association of adjuvant chemotherapy with improved survival among those with RS 26-30 and worse mortality associated with RS > 30 compared to RS 26-30.

Vertebral body collapse after spine stereotactic body radiation therapy: a single-center institutional experience.

BACKGROUND: Spine stereotactic body radiation therapy (SBRT) for the treatment of metastatic disease is increasingly utilized owing to improved pain and local control over conventional regimens. Vertebral body collapse (VBC) is an important toxicity following spine SBRT. We investigated our institutional experience with spine SBRT as it relates to VBC and spinal instability neoplastic score (SINS). PATIENTS AND METHODS: Records of 83 patients with 100 spinal lesions treated with SBRT between 2007 and 2022 were reviewed. Clinical information was abstracted from the medical record. The primary endpoint was post-treatment VBC. Logistic univariate analysis was performed to identify clinical factors associated with VBC. RESULTS: Median dose and number of fractions used was 24 Gy and 3 fractions, respectively. There were 10 spine segments that developed VBC (10%) after spine SBRT. Median time to VBC was 2.4 months. Of the 11 spine segments that underwent kyphoplasty prior to SBRT, none developed subsequent VBC. No factors were associated with VBC on univariate analysis. CONCLUSIONS: The rate of vertebral body collapse following spine SBRT is low. Prophylactic kyphoplasty may provide protection against VBC and should be considered for patients at high risk for fracture.

Re-Evaluating the Omission of Radiation Therapy in Low-Risk Patients With Early-Stage Breast Cancer.

Traditionally, management of early-stage breast cancer has required adjuvant radiation therapy following breast conserving surgery, due to decreased local recurrence and breast cancer mortality. However, over the past decade, there has been an increasing emphasis on potential overtreatment of patients with early-stage breast cancer. This has given rise to questions of how to optimize deintensification of treatment in this cohort of patients while maintaining clinical outcomes. A multitude of studies have focused on identification of a subset of patients with invasive breast cancer who were at low risk of local recurrence based on clinicopathologic features and therefore suitable for RT omission. These studies have failed to identify a subset that does not from RT with respect to local control. Several ongoing trials are evaluating alternative approaches to deintensification while focusing on tumor biology. With regards to ductal carcinoma in situ (DCIS), the role of RT has been questioned since breast conservation was utilized. Paralleling invasive disease studies, studies have sought to use clinicopathologic features to identify low risk patients suitable for RT omission but have failed to identify a subset that does not from RT with respect to local control. Use of new assays in patients with DCIS may represent the ideal approach for risk stratification and appropriate deintensification. At this time, when considering deintensification, individualizing treatment decisions with a focus on shared decision making is paramount.

Association of Neighborhood-Level Household Income With 21-Gene Recurrence Score and Survival Among Patients With Estrogen Receptor-Positive Breast Cancer.

Importance: While low income has been associated with a higher incidence of triple-negative breast cancer, its association with 21-gene recurrence score (RS) among patients with estrogen receptor (ER)-positive breast cancer remains unclear. Objective: To evaluate the association of household income with RS and overall survival (OS) among patients with ER-positive breast cancer. Design, Setting, and Participants: This cohort study used data from the National Cancer Database. Eligible participants included women diagnosed between 2010 and 2018 with ER-positive, pT1-3N0-1aM0 breast cancer who received surgery followed by adjuvant endocrine therapy with or without chemotherapy. Data analysis was performed from July 2022 to September 2022. Exposures: Low vs high neighborhood-level household income levels defined as below vs above the median household income of $50 353 based on each patient's zip code. Main Outcomes and Measures: RS (a score ranged from 0 to 100 based on gene expression signatures indicating the risk of distant metastasis, with RS of 25 or below indicating non-high risk and RS above 25 indicating high risk) and OS. Results: Among 119 478 women (median [IQR] age, 60 [52-67] years; 4737 [4.0%] Asian and Pacific Islander, 9226 [7.7%] Black, 7245 [6.1%] Hispanic, 98 270 [82.2%] non-Hispanic White), 82 198 (68.8%) and 37 280 (31.2%) patients had high and low income, respectively. Logistic multivariable analysis (MVA) showed that, compared with high income, low income was associated with higher RS (adjusted odds ratio [aOR], 1.11; 95% CI, 1.06-1.16). Cox MVA showed that low income was also associated with worse OS (adjusted hazards ratio [aHR], 1.18; 95% CI, 1.11-1.25). Interaction term analysis showed a statistically significant interaction between income levels and RS (interaction P < .001). On subgroup analysis, significant findings were noted among those with RS below 26 (aHR, 1.21; 95% CI, 1.13-1.29), while there was no significant OS difference between income levels among others with RS of 26 or higher (aHR, 1.08; 95% CI, 0.96-1.22). Conclusions and Relevance: Our study suggested that low household income was independently associated with higher 21-gene recurrence scores and significantly worse survival outcomes among those with scores below 26, but not 26 or higher. Further studies are warranted to investigate the association between socioeconomic determinants of health and intrinsic tumor biology among patients with breast cancer.

How to Treat a Tongue-tie: An Evidence-based Algorithm of Care.

Ankyloglossia, or tongue-tie, is characterized by a short or thickened lingual frenulum; this can be associated with impaired breastfeeding, speech, and dentofacial growth. The indications for performing frenotomy, frenuloplasty, or other operative interventions are unclear. METHODS: A meta-analysis was performed to identify the extent of the benefit from frenotomy in breastfeeding measures, degree of tongue-tie, and maternal pain during feeding in randomized controlled trials. A structured literature review analyzed the optimal type and timing of repair. An algorithm was developed to incorporate this evidence into a management pathway. RESULTS: Among 424 studies reviewed, 5 randomized controlled trials met inclusion criteria for meta-analysis. Frenotomy significantly improved the degree of tongue-tie, with a 4.5-point decrease in Hazelbaker Assessment Tool for Lingual Frenulum Function score compared with a decrease of 0 in those who did not undergo frenotomy (P < 0.00001). This was associated with improved self-reported breastfeeding (relative risk [RR] = 3.48, P < 0.00001) and decreased pain (Short-Form McGill Pain Questionnaire, P < 0.00001); however, Breastfeeding Self-Efficacy-Short Form and Latch, Audible Swallowing, Type of Nipple, Comfort, Hold scores did not significantly improve. Multiple studies demonstrated significant improvements following frenuloplasty when compared with frenotomy but demonstrated mixed results as to the effect of timing of tongue-tie division. CONCLUSIONS: Frenotomy is associated with breastfeeding improvements that vary individually but trend toward significance collectively during a critical time in infant development. Among patients with a severe Hazelbaker Assessment Tool for Lingual Frenulum Function score or difficulty breastfeeding, we conclude that simple frenotomy without anesthetic is generally indicated in infancy and frenuloplasty under general anesthesia for older children.

Vascularized Rib Bone Grafting: Indications, Techniques, and Clinical Outcomes.

Pseudarthrosis is a difficult complication often seen in patients with complex spinal pathology. To supplement existing neurosurgical approaches to cervicothoracic spinal instrumentation and fusion, novel vascularized rib bone grafts can be utilized in patients at high risk for failed spinal fusion. In this article, we discuss the indications, benefits, surgical technique, feasibility, and limitations of using rib vascularized rib bone grafts to augment spinal fusion.

Vascularized Bone Grafts for Spinal Fusion-Part 2: The Rib.

BACKGROUND: Pseudoarthrosis, or failure to achieve bony union, is a well-known complication of spinal fusion operations. Rates range from 5% to 40% and are influenced by both patient and technical factors. Patients who do not achieve complete fusion may experience a return or worsening of their preoperative pain. For patients with complicated pathologies, vascularized bone grafts (VBGs) have been shown to provide better outcomes than nonvascularized bone grafts (N-VBGs). OBJECTIVE: To enhance an instrumented spinal fusion by the innovative technique presented herein that utilizes a rotated, pedicled VBG from the left eighth rib under the paraspinous musculature into the midlumbar posterolateral gutter. METHODS: For posterior approaches, the rib can be easily accessed and rotated into the appropriate strut position. The rib is dissected out, identifying and preserving the neurovascular bundle medially. The rib is then tunneled medially and appropriately positioned as the spinal graft, with the curve providing anatomic kyphosis or lordosis, depending on the surgical location. It is then successfully fixated with plates and spinal screws. RESULTS: In our limited experience to date, vascularized rib grafting procedures augment fusion and reduce operating room time and bleeding compared to free flap procedures. No patients have experienced complications related to these grafts. CONCLUSION: Pedicled vascularized rib grafts can be utilized to provide the advantages of a vascularized bone flap in complicated pathologies requiring spinal fusion as far as the L2-L3 level, without the morbidity associated with free tissue transfer.

Nodal positivity in breast cancer correlated with the number of lesions detected by magnetic resonance imaging versus mammogram.

BACKGROUND: Magnetic resonance imaging (MRI) in breast cancer can detect more than 15% additional lesions than mammography. We investigated lymph node metastases rates in patients with multifocal or multicentric disease detected by MRI compared with patients with a single lesion detected by mammography and magnetic resonance imaging. METHODS: A retrospective analysis of breast cancer patients undergoing MRI and mammography was performed. The objective was to compare lymph node metastases rates in patients with additional lesions detected by MRI versus a single lesion detected by mammography or MRI. RESULTS: Of 413 patients, 318 were included for the study. The overall nodal metastases rate was 24.8%. MRI detected multiple lesions in 83 (26.1%) patients; 67 (21.1%) patient MRI findings were not detected by mammography. The lymph node metastases rate was 37.3% when ≥ 2 lesions were detected compared with 20.2% when a single malignant lesion was detected (P = .01). The evaluation of the 67 patients with additional lesions detected by MRI revealed 32 patients with invasive lesions, 29 with benign lesions, and 6 with in situ disease. Comparing patients with single malignant lesions with patients with additional malignant lesions detected by MRI, the lymph node metastases rate increased from 20.2% to 50% (P = .002). CONCLUSIONS: Our study shows a significant increase in the lymph node metastases rate in patients with additional malignant lesions detected by MRI. This finding suggests that MRI-detected malignant lesions are biologically significant and may predict more aggressive disease.