Approximately 25 % of patients with TNBC experienced a locoregional and/or distant recurrence, resulting in greater than 75 % breast cancer-specific mortality for those who experienced a distant recurrence. The lack of targeted therapy for this aggressive breast cancer subtype likely contributed to this finding.
◥Purpose: Treatment of advanced melanoma is a clinical challenge. Natural killer (NK) cells are a promising cellular therapy for T cellrefractory cancers, but are frequently deficient or dysfunctional in patients with melanoma. Thus, new strategies are needed to enhance NK-cell antitumor responses. Cytokine-induced memory-like (ML) differentiation overcomes many barriers in the NK-cell therapeutics field, resulting in potent cytotoxicity and enhanced cytokine production against blood cancer targets. However, the preclinical activity of ML NK against solid tumors remains largely undefined.Experimental Design: Phenotypic and functional alterations of blood and advanced melanoma infiltrating NK cells were evaluated using mass cytometry. ML NK cells from healthy donors (HD) and patients with advanced melanoma were evaluated for their ability to produce IFNg and kill melanoma targets in vitro and in vivo using a xenograft model.Results: NK cells in advanced melanoma exhibited a decreased cytotoxic potential compared with blood NK cells. ML NK cells differentiated from HD and patients with advanced melanoma displayed enhanced IFNg production and cytotoxicity against melanoma targets. This included ML differentiation enhancing melanoma patients' NK-cell responses against autologous targets. The ML NK-cell response against melanoma was partially dependent on the NKG2D-and NKp46-activating receptors. Furthermore, in xenograft NSG mouse models, human ML NK cells demonstrated superior control of melanoma, compared with conventional NK cells.Conclusions: Blood NK cells from allogeneic HD or patients with advanced melanoma can be differentiated into ML NK cells for use as a novel immunotherapeutic treatment for advanced melanoma, which warrants testing in early-phase clinical trials.
Abstract. Nipple-sparing mastectomies (NSMs) are increasingly used in the surgical treatment of patients with breast cancer and for prevention of breast cancer. The present study was performed to review the outcomes of patients undergoing NSMs at a single large university setting. A retrospective chart review was performed on all patients undergoing NSMs from 2008-2014. Charts were reviewed for demographic data and patient characteristics. Tumor and breast size, cancer recurrence and complications were also evaluated. Descriptive statistics were utilized to summarize the findings. From 2008From -2014 NSMs. The mean patient age was 44.4 years (range, 20-77). The average body mass index was 24 (range, 18-47). Breast weight was available for 106 specimens, with a mean weight of 475.5 g (range, 124.1-1,625.0 g). Seventy-three NSMs were performed for cancer and 124 were performed prophylactically. The mean tumor width was 1.38 cm (range, 0-6.0 cm), with an average nipple to tumor distance of 5.87 cm (range, 2.93-10.0 cm). Three (4%) patients required removal of the nipple areolar complex (NAC) due to pathological extension of the tumor. A total of 34 (17.2%) complications occurred, including infections, hematomas and nipple necrosis, with 9 requiring removal of the NAC and 13 requiring removal of the tissue expander or implant. Smokers had a 36.0% (9/25) complication rate, compared with 14.5% (25/172) of nonsmokers (P<0.05). During follow-up, one recurrence was noted, located on the chest wall. There were no recurrences in the NAC group. Therefore, NSMs may safely be performed without compromising oncologic outcomes or increasing complication rates in properly selected patients.
IntroductionWe describe a novel device for rapid and economical minimal erythema dose testing in patients undergoing ultraviolet (UV) light phototherapy for treatment of skin diseases.MethodsA minimal erythema testing device was designed and created using transparent plastic sheeting and printed patterns with increasing ink density, allowing for graded UV transmission of 100%, 80%, 60%, 40%, 20%, and 10% energy through six 10-mm square apertures. The plastic sheet was placed in a UV-impenetrable and Velcro-fitted adjustable sleeve, designed to fit easily onto a patient’s arm. A pilot validation study was performed, comparing this device with a commercially available windowed device in which the dose is controlled by varying the UV exposure time through sequential opening of each window. The pilot was conducted on healthy skin of two human subjects with different Fitzpatrick skin types.ResultsIn our subjects, tested with one device on each forearm, the minimal erythema dose (MED), judged visually, was identical. However, the test device allowed MED testing in 3 min compared with 15 min for the traditional device. The test device is equally effective for use with ultraviolet-A (UVA), narrowband ultraviolet-B (NB-UVB) and broadband ultraviolet-B (BB-UVB) wavelengths. The test device is economical, with manufacturing cost of less than US $2.ConclusionWe designed an MED testing device that is quick, accurate, cost-effective, and easy to use in the setting of a busy phototherapy practice. This device therefore has many advantages over existing MED testing approaches.
Background: It is estimated that approximately 46,000 women age >75 are diagnosed annually with breast cancer. Due to competing co-morbidities, there is wide variation in treatment recommendations which can lead to over- or under-treatment. Though surgery for breast cancer is considered low-morbidity, many elderly women given a choice, choose not to have surgery. Previous randomized trials comparing surgery with tamoxifen versus endocrine therapy alone in women age >70 unselected for ER status demonstrated similar overall survival with poorer local control in the latter group. A new standard of care needs to be defined for elderly women with good prognosis ER+ tumors, since these women may benefit from endocrine therapy alone to treat their cancer without compromising local and distant control. Hypothesis: We hypothesize that endocrine therapy alone provides adequate local and systemic control of breast cancer in a subpopulation of women age 70 or older with ER+ breast cancer and good prognostic characteristics. Primary Objective To correlate response to neoadjuvant endocrine treatment at 6 months with Oncotype DX Recurrence Score (RS) in women with early-stage ER+ breast cancer who are age >70. Secondary Objective 1. To determine the breast cancer-specific survival of women with early-stage ER+ breast cancer, age >70, treated with endocrine therapy alone. 2. To determine the rate of overall survival of women with early-stage ER+ breast cancer, age >70 treated with endocrine therapy alone. Study Design: This is a prospective single arm phase II study. Patients with clinical stage I/II ER+ breast cancer, grade 1-2, Ki67<30 or RS <18 (performed on the diagnostic core biopsy) continue to be enrolled and followed for time to progression. A Kaplan-Meier model will be used to estimate the 5-year local progression rate. If the true 5-year progression rate is 10%, then 50 patients will provide power = .90 at a one-sided .05 significance level to demonstrate that the rate is less than 25.5%. Exploratory objectives include: evaluation of the molecular characteristics of breast cancers of responders versus non-responders, determine compliance with medications, evaluate cost-effectiveness, and quality of life. Results: Between February 2017 and April 2018, 11 patients were enrolled into the study. Two patients could not tolerate endocrine therapy and received standard of care treatment. For the 9 patients on study, average tumor size was 1.7cm, average Ki67 was 15%, average RS was 14. All of the patients received an aromatase inhibitor. At 6 months, 71% of the patients had a partial response, 28% had stable disease. None of the patients developed progressive disease. Conclusion: A new standard of care needs to be defined for women age >70 with good prognosis ER+ tumors, since these women may benefit from endocrine therapy alone to treat their cancer without compromising local and distant control. We continue to enroll patients to determine the optimal tumor markers for identifying women who can be treated with PET only to control their cancer. Citation Format: Aft R, Cherian M, Frith A, Suresh R, Glover-Collins K, Naughton M, Moon C, Conant L, Ma C. Endocrine treatment alone as primary treatment for elderly patients with estrogen receptor positive good prognosis operable breast cancer: A single arm phase II, single institution study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-01-05.
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