Magnetic resonance imaging (MRI) accuracy after neoadjuvant systemic therapy (NST) for breast cancer varies according to hormone receptor (HR), human epidermal growth factor receptor type-2 (HER2) subtype and Ki-67 proliferation index. Whether MRI accuracy varies by genomic signatures is unknown. We examined the accuracy of MRI in the NEONAB trial (Clinicaltrials.gov #: NCT01830244).To examine the accuracy of MRI to predict pathological response to neoadjuvant therapy for breast cancer in the NEONAB trial.Patients with stages II-III breast cancer received sequential epirubicin, cyclophosphamide and nab-paclitaxel and trastuzumab if they were HER2+. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated to assess the utility of preoperative MRI to predict pathological complete response (pCR). Bland-Altman plots were used to assess agreement between MRI and pathological assessment of residual disease.MRI correctly predicted pCR in 64.1% of the cohort. Sensitivity and specificity were 52% and 78%, respectively; PPV 73% and NPV 58%. MRI predicted pCR most accurately in HER2-positive patients; sensitivity 58%, specificity 100%, PPV 100% and NPV 38%. MRI had higher PPV and NPV in tumours with Ki-67 ≥ 15% than tumours with Ki-67 < 15%, 75% versus 50% and 57.5% versus 50%, respectively. In this study, MRI underestimated residual tumour size by 1.65 mm (limits of agreement: 43.07-39.77 mm).MRI appears more accurate for predicting pCR in HER2+ disease than other subtypes and in cancers with Ki-67 ≥ 15% compared to those with Ki-67 < 15%. Accuracy of MRI in our HR+, RS ≥ 25 cohort is comparable to previous reports of unselected HR+ disease. MRI post-NST should be interpreted in conjunction with HER2 status and Ki-67 index of the primary.
e12515 Background: We evaluated the feasibility and the likelihood of achieving high response rates by tailoring neoadjuvant therapy based on individual patient and tumor characteristics. Triple negative (TNBC) and HER2+ pts were treated with chemotherapy. Hormone Receptor (HR)+ HER2- pts were treated based on the Oncotype DX Breast Recurrence Score (RS) result. Methods: Between 4/2013 and 1/2015, 40 pts with stage II (T > 2cm) or III were enrolled: 15 HER2+, 15 TNBC and 10 with HR + HER2- breast cancer with RS ≥25. HR+ HER2-tumors with RS <25 were treated in an exploratory cohort. The primary cohort (n=40) was treated with preoperative epirubicin 90mg/m2 and cyclophosphamide 600mg/m2 Q3 weeks x 4, followed by nab-P (125mg/m2days 1, 8, 15 Q4 weeks) for 12 weeks, with the addition of trastuzumab in HER2+ pts. The primary endpoint was pCR in breast (ypT0/ypTis). A single stage binomial design was planned to discriminate between overall pCR rates of 30 and 50% with a type I error of 6% and 87% power. Secondary endpoints included pCR in breast and lymph nodes (LN), toxicity, PFS, and translational endpoints using pre- and post-chemotherapy MRIs and tissue biomarker analysis. An independent data safety board assessed trialsafety. Clinicaltrials.gov: NCT01830244. Results: Median age was 50 yrs (34 – 76). Clinical stages were T2 (67.5%), T3 (25%), T4 (7.5%), N0 (32.5%), N1 (40%), N2 (22.5%) and N3 (5%). LN involvement was confirmed with biopsy in 20 of 27 pts with N1 – N3. Breast conservation rate was 48% (n=19). Overall pCR rate in the breast was 55% (n=22). pCR rate in subsets is shown below pCR %(n): See table. Grade 3/4 Adverse Events (AEs): febrile neutropenia (8%), neutropenia (18%), sensory neuropathy (5%), deranged transaminases (5%), fatigue (2%), diarrhea (2%), pneumothorax (2%). Common grade 1/2 AEs: alopecia (95%), fatigue (68%), nausea (57%), neutropenia (57%) and neuropathy in (50%). Conclusions: This EC and nab-P regimen resulted in a high rate of pCR, demonstrating that tailored neoadjuvant therapy including patient selection by OncotypeDX is feasible and warrants further investigation. Clinical trial information: NCT01830244. All (40) HER2+ (15) TNBC (15) HR+ HER2- RS ≥25 (10) Breast 55 (22) 80 (12) 46 (7) 30 (3) Breast & LN 48 (19) 80 (12) 40 (6) 10 (1)
Calcification within multiple lung opacities in a radiograph is usually considered strong evidence in favour of a tuberculous aetiology, but it may occur in metastases from an osteogenic sarcoma (Speed, 1943).The following two cases illustrate that similar calcification may occasionally occur in slowly growing or "quiescent" pulmonary metastases from other tumours..
To investigate the role of mast cells in surgical and pathological scar reactions by their identification and quantification using immunohistochemistry.
METHODS
Surgical scars and pathological scar reactions were stained immunohistochemically for tryptase to identify mast cells. These were quantified in the scar tissue and surrounding dermis. Statistical analyses were performed to test the hypothesis that mast cell numbers were different in the varying types of scar reaction.
RESULTS
A significant difference was found between the mean number of mast cells in periocular scars compared with keloids, hypertrophic scars, and surgical scars from other sites (p<0.05). No significant difference was found in mast cell numbers between the other scar types either within the lesions or surrounding dermis. There were significantly more mast cells in the dermis than in the scar tissue itself, except for the small group of periocular scars. The ratio of mast cells in the lesion compared with the dermis was not significantly different between the scar types, except for the periocular scars.
CONCLUSIONS
Mast cell numbers are similar in and around keloid, hypertrophic, and surgical scars. The increased number of mast cells at periocular scar sites was contrary to expectation since keloids are rare at this site. Absolute mast cell numbers may not be an accurate measure of tissue concentrations of active mast cell products. Further comparisons between immunological characteristics of keloid and periocular scars may elucidate specific immunological abnormalities of keloid scars, and this has implications for the development of immunotherapy.
TPS1135 Background: Neoadjuvant chemotherapy for breast cancer allows response to be assessed depending on subtype, and to judge impact of response to therapy on progression-free survival (PFS). Methods: This study enrols women with breast tumours > 2cm and high likelihood of response, to receive Epirubicin 90mg/m2 and Cyclophosphamide 600mg/m2 Q3 weeks x 4 followed by nab-Paclitaxel (125mg/m2 IV days 1, 8, 15 Q4 weeks) for 12 weeks. Trastuzumab Q3 weeks, will be added to nab-paclitaxel in HER2 positive patients. Forty women; 15 HER2 positive, 15 triple negative and 10 patients with Oncotype DX assay Recurrence Score (RS) >25 will be evaluated for response. We will screen 50 hormone positive women to identify 10 with Oncotype DX assay RS ≥25 and the patients with RS <25 will be included as an exploratory cohort to receive neoadjuvant hormonal treatment. The primary endpoint is rate of pathologic Complete Response (pCR) in the breast. In previous studies, Response Rate (RR) ranged from 12 to 30%. Accordingly, we set RR rate for the null hypothesis (uninteresting) at 30% and for the alternative (worthy of further study) at 50% (CI 95%). Forty patients will be evaluated to discern between RR of 30% and 50% (6% type I error and 87% power). If at the end of the study, 17 or more patients achieve pCR, the regimen will be deemed worthy of further study. Secondary end points include rate of breast conservation, safety and tolerability, PFS and a number of translational endpoints using pre- and post-chemotherapy MRIs and tissue. Translational endpoints include determination of NQO1*2 genotype (P187S) status that may predict anthracycline resistance, isolating cancer stem cells, passing fresh tumour to xenograft, implanting tumours, using aptamers to target implanted tumours and targeting breast cancer stem cells with novel agents including cyclin D and histone deacetylatase inhibitors. Current status: Recruitment began April 2013. A total of 20 patients have been enrolled on to the study as of Feb 2014. Clinical trial information: NCT01830244.
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