Search

Supplemental Figure 5. Ki67 Change was not associated with drug concentration in Tumor samples. Tumor samples were available for quantitation from 22 women.

Supplemental Figure 2. Ki67 Change relative to treatment duration. There was no significant correlation between change in Ki67 and treatment duration, in either TPA or placebo arms.

Supplemental Figure 4. Plots showing changes in serum estradiol (left panel) and serum progesterone (right panel) in three subgroups: placebo, TPA-treated Ki67 responders and TPA-treated Ki67-nonresponders.

Supplemental Figure 3. Validation of RNA seq results of responders by Nanostring nCounter gene expression assay

Supplemental table 2. Differential gene expression and pathway enrichment analysis in placebo responders (excel file) -uploading separately.

Supplemental table 1. Differential gene expression and pathway enrichment analysis in TPA responders (excel file) -uploading separately.

Supplemental table 3. Nanostring nCounter Differential gene expression (excel file) -uploading separately.

Purpose:Selective progesterone receptor modulators (SPRMs) show preclinical activity against hormone-sensitive breast cancer, but have not been tested in patients with early, treatment-naïve tumors.Patients and Methods:In a double-blind presurgical window trial of oral telapristone acetate (TPA) 12 mg daily versus placebo, 70 patients with early-stage breast cancer were randomized 1:1 (stratified by menopause) and treated for 2 to 10 weeks. The primary endpoint was change in Ki67 between diagnostic biopsy and surgical specimens. Gene expression pre- and posttherapy was assessed using RNA-sequencing and gene set enrichment analysis was performed to determine pathways enriched in response to TPA and placebo treatments.Results:Among 61 evaluable women (29 placebo and 32 telapristone acetate), 91% of tumors were ER/PR positive. The mean Ki67 declined by 5.5% in all women treated with telapristone acetate (P = 0.003), and by 4.2% in all women treated with placebo (P = 0.04). After menopausal stratification, the Ki67 decline remained significant in 22 telapristone acetate–treated premenopausal women (P = 0.03). Differential gene expression analysis showed no significant modulation overall. However, in a subset of tumors that demonstrated ≥30% relative reduction in Ki67 in the telapristone acetate group, genes related to cell-cycle progression, and those in the HER2 amplicon were significantly downregulated. In contrast, no significantly enriched pathways were identified in the placebo group.Conclusions:Patients treated with telapristone acetate whose Ki67 decreased by ≥30% demonstrated a selective antiproliferative signal, with a potentially important effect on HER2 amplicon genes. Evaluation of SPRMs in a neoadjuvant trial is merited, with attention to predictors of response to SPRM therapy, and inclusion of pre- and postmenopausal women.

Supplemental Materials Supplemental Table 4. Changes in serum sex hormone concentrations according to the treatments. Supplemental Table 5. Summary of BESS Quality of Life Assessment by symptom clusters according to the treatments Supplemental Table 6. Summary of Adverse Effects.

Supplemental Figure 1. Validation of RNA seq results of responders by Nanostring nCounter gene expression assay.

En analyse og sammenligning av bestemmelsene om erstatningsverneting i Luganokonvensjonen artikkel 5 nr. 3 og tvisteloven § 4-5 tredje ledd.

e18032 Background: The IOM ’11 and ’13 reports recommend a written care plan (WCP) at cancer diagnosisto enable teamwork and patient (pt) engagement. Standardized multimodality WCP is a key part of the 4R model of care planning and pt engagement proposed under “NCI ASCO Teams” Project (Trosman JOP 2016). 4R (Right Information / Care / Patient / Time) is under implementation at 3 centers: academic, community and safety net. As current state assessment prior to implementing 4R and standard multimodality WCP, we surveyed pts not impacted by 4R on care planning, enablement and whether they received any WCP. Methods: Survey of breast cancer stage I-III pts who received care at the three sites Jan ’15 - Mar ’16, prior to 4R. We used simple frequencies and Fisher’s exact test in analysis. Results: Survey response rate: 47%, 241/515. Gaps of > 30% were reported in 7 of 8 aspects of care planning and pt enablement - Table. A non standard WCP was received by 46% of pts. Receiving a WCP impacted whether pts were clear about care (85% with WCP vs 52% without, p < .0001), able to manage own care (79% with WCP vs 58% without, p = .0005) and overwhelmed (35% with WCP vs 49% without, p = .04). Care complexity was a significant factor for feeling overwhelmed by pts without WCP (49% of pts receiving > 6 care services felt overwhelmed vs. 30% of pts receiving < = 6 services, p = .04), but not a significant factor in pts with WCP (45% vs 41%, p = .7). More pts with WCP reported well managed care by providers than pts without WCP (77%, 62%, P = .02). Conclusions: Serious gaps found in care planning and pt enablement at our sites support the need for 4R implementation. Even pre-4R, non standard WCPs improve pt understanding of care and ability to manage it, and reduce the impact of care complexity on pts. Providers using WCP appear to also coordinate care, but WCP itself may be an important factor of patient enablement. [Table: see text]

e12067 Background: The “NCI ASCO Teams” Project emphasized management of interdependent cancer care across specialties as crucial to teamwork, yet a considerable challenge (Taplin JOP 2015). Interdependent care requires well-managed timing and sequencing of events across specialties. We developed the 4R model (Right Information / Care / Patient / Time) to manage interdependent care and facilitate teamwork (Trosman JOP 2016). 4R is being implemented at 3 centers: academic, community and safety net. Pre-implementation, we identified guideline recommended interdependent care whose timing / sequencing is challenging, developed relevant adherence metrics and gathered current state data. Methods: Interviews with 42 clinicians across breast cancer (BC) specialties at the 3 sites, using theme analysis to identify challenging interdependent care. Guidelines and literature were used to define adherence metrics. Clinical data were reviewed for 216 Stage I-III patients at 3 sites to measure adherence. Results: We identified 7 BC interdependent care events for which timing / sequencing is a challenge - Table. Adherence ranged from 0% to 100%, and was < 50% for 5 of the 7 care events. Preoperative BRCA 1/2 results and neoadjuvant consult showed highest adherence, yet were most frequently noted as a challenge: interviewees reported substantial ad-hoc efforts applied to managing timeliness of these events. Conclusions: Identified challenges and adherence gaps support the need for the 4R implementation for systematic, consistent and timely delivery of interdependent care. Established metrics will allow pre / post 4R implementation comparison and may inform broader adoption of the 4R model. [Table: see text]

BACKGROUND Widespread use of mammography has increased the detection of ductal carcinoma in situ with microinvasion (DCISM) in pathology specimens. Currently there is disagreement regarding the incidence of axillary metastasis from DCISM. The controversy centers on whether complete lymphadenectomy is indicated for axillary staging, given its morbidity and the reportedly minimal rate of axillary involvement in these patients. Intraoperative lymphatic mapping and sentinel lymphadenectomy (SLND) may obviate complete axillary lymph node dissection in selected breast carcinoma patients. In intraoperative lymphatic mapping, isosulfan blue dye is used to demonstrate the course of lymphatic flow from the breast tumor to the first draining or sentinel lymph node. This blue-stained lymph node is selectively excised for pathologic examination; its tumor status is used to predict the tumor status of the other axillary lymph nodes. The authors examined whether SLND would be suitable for staging DCISM. METHODS From February 1992 to January 1997, 14 patients with DCISM underwent intraoperative lymphatic mapping and SLND at the John Wayne Cancer Institute in Santa Monica, California. Clinical and pathologic data were prospectively collected. RESULTS Primary DCISM tumors ranged in size from 0.9 to 6.5 cm. Nine patients presented with mammographic abnormalities, two patients presented with Paget's disease and a palpable lesion, and three patients presented with palpable lesions. Two patients (14.3%) had tumor-involved sentinel lymph nodes. One of these patients had two sentinel lymph nodes, both of which contained single cancer cells identified by immunohistochemistry. The other patient had 1 sentinel lymph node, in which a 0.3-cm metastasis was revealed by light microscopy. Completion axillary dissection was performed on both patients and revealed no further tumor positive lymph node metastases. CONCLUSIONS SLND can detect lymph node micrometastases (tumor deposits