Locoregional and Distant Outcomes in Women With cT1-3N1 Breast Cancer Treated With Neoadjuvant Chemotherapy With or Without Adjuvant Radiotherapy.

BACKGROUND: We evaluated the impact of postmastectomy radiotherapy (PMRT) or supraclavicular radiation therapy (SCV RT) in women with cT1-3N1 breast cancer (BC) who became node negative (ypN0) after neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: We retrospectively reviewed 485 women treated with NAC for BC between 2005 and 2019. Radiation treatment fields were reviewed in detail. Pathologic complete response (pCR) was defined as ypT0/Tis ypN0. Patients who had residual nodal disease were defined as ypN+. Those who achieved complete response in the lymph nodes but not in the breast were defined as ypT+ypN0. RESULTS: After excluding patients with cT4 and cN0 disease at diagnosis, a total of 185 patients with cT1-3N1 BC were included. Patients were more likely to receive PMRT if they had ypN+ disease (P < .001) and/or lymphovascular invasion (P = .03). Patients who underwent lumpectomy were more likely to receive SCV RT if they did not achieve pCR (P = .04) and/or if they had ypN+ disease (P = .01). The 5-year rates of locoregional recurrence (LRR) were 15% for all patients, 14% for patients who attained ypT+ypN0, and 5% for patients who achieved pCR. Of ypT+ypN0 patients (n = 98), 53 received PMRT or SCV RT and 45 did not. For these patients, there were no differences in LRR based on whether a patient did or did not receive PMRT or SCV RT (P = .23). CONCLUSION: Recommendations for or against PMRT or SCV RT after NAC vary based on final pathologic response. We await the results of ongoing randomized clinical trials to help guide clinical decision making in this context.

Patterns of Failure in Women Who Have Residual Nodal Disease After Neoadjuvant Chemotherapy for Breast Cancer According to Extent of Lymph Node Surgery.

BACKGROUND: Optimal surgical management of limited axillary nodal disease following neoadjuvant chemotherapy (NAC) for breast cancer is evolving. Concerns exist with respect to leaving residual disease in the axilla when omitting axillary lymph node dissection (ALND) in this setting. We sought to determine whether extent of nodal surgery altered patterns of failure and patient outcomes. PATIENTS AND METHODS: We identified 70 patients with breast cancer who were confirmed cN0 after NAC yet had residual nodal disease (ypN1) on sentinel lymph node biopsy (SLNB). Twenty-eight patients underwent SLNB alone and 42 underwent SLNB+completion (c)ALND in a non-randomized fashion. Most (n = 65) patients underwent adjuvant regional nodal irradiation (RNI). Detailed patterns of failure data were obtained for each patient. RESULTS: The median follow-up was 43.5 months. There were 30 (43%) recurrences. Of these, 5 were isolated locoregional failures, and 24 were distant failures. There were no significant differences in local (P = .13), regional (P = .62), or distant (P = .47) failure between patients who underwent SLNB alone versus SLNB+cALND. Seventeen (24%) patients died. Overall survival was similar in both groups with median overall survival not reached for those who underwent SLNB and 109 months for those who underwent SLNB+cALND (P = .45). CONCLUSIONS: There were no differences in patterns of recurrence among patients with 1 to 3 involved lymph nodes after NAC who underwent SLNB alone versus SLNB+cALND in the setting of RNI. We await the results of ongoing, prospective clinical trials to confirm the relative merits of RNI in lieu of cALND in these patients.

The MarrowMiner: A Novel Minimally Invasive and Effective Device for the Harvest of Bone Marrow.

Bone marrow (BM) is a rich source of hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), and other important stem/progenitor cells. It is the traditional source of cells used in hematopoietic cell transplantation, which is a proven curative treatment for many blood and immune diseases. BM-derived cells have also been shown to have other diverse clinical uses and are increasingly being used in orthopedic medicine, regenerative medicine, and gene therapy applications. Traditional methods for harvesting BM are crude, tedious, time-consuming, and expensive, requiring multiple bone punctures under general anesthesia with serial small-volume aspirates often diluted with peripheral blood. The MarrowMiner (MM) is a novel device designed for rapid and minimally invasive BM harvest. Here we show the safety and efficacy of the MM in both preclinical and clinical settings. In a large-animal porcine model, the MM enabled effective BM collection with similar total nucleated cell collection and increased colony formation compared with standard methods. The MM was subsequently evaluated in a clinical study showing effective and complication-free anterior and posterior BM collection of 20 patients under only local anesthesia or light sedation. Increased total nucleated and mononucleated cell collection was achieved with the MM compared with standard methods in the same patients. Importantly, stem cell content was high with trends toward increased HSC, MSC, and endothelial progenitor cells with similar T cell content. Given the MM is a novel device approved by the US Food and Drug Administration, enabling safe, effective, and minimally invasive harvest of BM, we anticipate rapid adoption for various applications.

Selective hematopoietic stem cell ablation using CD117-antibody-drug-conjugates enables safe and effective transplantation with immunity preservation.

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for blood and immune diseases with potential for many settings beyond current standard-of-care. Broad HSCT application is currently precluded largely due to morbidity and mortality associated with genotoxic irradiation or chemotherapy conditioning. Here we show that a single dose of a CD117-antibody-drug-conjugate (CD117-ADC) to saporin leads to > 99% depletion of host HSCs, enabling rapid and efficient donor hematopoietic cell engraftment. Importantly, CD117-ADC selectively targets hematopoietic stem cells yet does not cause clinically significant side-effects. Blood counts and immune cell function are preserved following CD117-ADC treatment, with effective responses by recipients to both viral and fungal challenges. These results suggest that CD117-ADC-mediated HSCT pre-treatment could serve as a non-myeloablative conditioning strategy for the treatment of a wide range of non-malignant and malignant diseases, and might be especially suited to gene therapy and gene editing settings in which preservation of immunity is desired.

Patterns of Distant Failure by Intrinsic Breast Cancer Subtype in Premenopausal Women Treated With Neoadjuvant Chemotherapy.

PURPOSE: To identify patterns of distant failure (DF) in premenopausal women receiving neoadjuvant chemotherapy (NAC) for breast cancer. PATIENTS AND METHODS: Premenopausal patients treated with NAC between 2005 and 2015 at a single institution were retrospectively reviewed. Timing and location of local, regional, and distant metastases were described. Predictors for DF and overall survival (OS) were analyzed. RESULTS: Of 225 patients, there were 24 (10.7%) local, 30 (13.3%) regional, and 63 (28.0%) distant recurrences. Cumulative incidence of DF was higher in patients younger than age 40 (P = .01), in those with residual tumor size > 2 cm (P < .0001), in those with positive lymph nodes after NAC (P = .0003), and in those without pathologic complete response (P < .0001). Cumulative incidence of brain metastases was most common in patients with human epidermal growth factor receptor 2 (HER2)-positive disease (P = .05). Time from development of metastatic disease to death varied by breast cancer subtype (P = .019), as did 5-year OS (P = .024). Women with HER2-positive and triple-negative disease had the highest incidence of brain metastases and the shortest time from development of metastases to death. On multivariable analysis, luminal B subtype (P = .025), pathologic complete response (P = .0014), young age (P = .0008), lack of hormone therapy (P < .0001), lymphovascular space involvement (P < .0001), and pathologic size of the primary tumor (P < .0001) were all significant predictors for DF. CONCLUSION: Patterns of DF after NAC in premenopausal women vary by breast cancer subtype, with DF more common than locoregional failure. Young age remains an independent poor prognostic factor, and OS differs by breast cancer subtype.