Jamie Lynn Wagner

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts

Purpose: Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin to anthracycline/taxane chemotherapy improves pathologic complete response (pCR) in triple-negative breast cancer (TNBC). Effectiveness of anthracycline-free platinum combinations in TNBC is not well known. Here, we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC. Experimental Design: The study population includes 190 patients with stage I–III TNBC treated uniformly on two independent prospective cohorts. All patients were prescribed NA chemotherapy regimen of carboplatin (AUC 6) + docetaxel (75 mg/m2) given every 21 days × 6 cycles. pCR (no evidence of invasive tumor in the breast and axilla) and residual cancer burden (RCB) were evaluated. Results: Among 190 patients, median tumor size was 35 mm, 52% were lymph node positive, and 16% had germline BRCA1/2 mutation. The overall pCR and RCB 0 + 1 rates were 55% and 68%, respectively. pCRs in patients with BRCA-associated and wild-type TNBC were 59% and 56%, respectively (P = 0.83). On multivariable analysis, stage III disease was the only factor associated with a lower likelihood of achieving a pCR. Twenty-one percent and 7% of patients, respectively, experienced at least one grade 3 or 4 adverse event. Conclusions: The CbD regimen was well tolerated and yielded high pCR rates in both BRCA-associated and wild-type TNBC. These results are comparable with pCR achieved with the addition of carboplatin to anthracycline–taxane chemotherapy. Our study adds to the existing data on the efficacy of platinum agents in TNBC and supports further exploration of the CbD regimen in randomized studies. Clin Cancer Res; 23(3); 649–57. ©2016 AACR.

Impact of neoadjuvant chemotherapy on axillary nodal involvement in patients with clinically node negative triple negative breast cancer.

We evaluated the impact of Neoadjuvant Chemotherapy (NAC) versus primary surgery (PS) on axillary disease burden/surgery in clinically node negative Triple Negative Breast Cancer (TNBC).

Abstract P3-06-16: Thrombocytopenia is associated with pathological complete response to neoadjuvant carboplatin/docetaxel chemotherapy in BRCA wild type triple negative breast cancer

Introduction: Growing evidence demonstrates activity of neoadjuvant carboplatin in triple negative breast cancer (TNBC). Underlying germline and somatic Homologous Recombination (HR) repair deficiency may predict response to DNA damaging agents like platinum compounds in TNBC. Certain DNA repair machinery genes (Fanconi Anemia gene) are also involved in the maintenance of hematopoetic stem cell (HSC) function and impaired repair of DNA double strand breaks can lead to HSC and progenitor cell dysfunction. Thus, in presence of HR defects DNA damaging chemotherapy may lead to unique hematological toxicity. It is also possible that in presence of HR defects breast cancer response and hematological toxicity with DNA damaging agents will parallel each other. Aim: To evaluate the impact of hematological toxicity on response to neoadjuvant Carboplatin/Docetaxel chemotherapy in patients with sporadic and BRCA associated TNBC utilizing clinical and BRCA mutation data from a prospective TNBC registry. Methods: 288 patients with Stage I (T>1cm) II and III TNBC were enrolled on a multisite prospective registry between 3/2011 to 4/2014, out of which 49 patients received neoadjuvant Carboplatin AUC 6 + Docetaxel 75mg/m 2 every 21 days (4-6 cycles) and have undergone breast surgery. Carboplatin was dosed using the modified Cockcroft-Gault formula. Hematologic toxicity was graded using the CTCAE version 4.03. All patients received prophylactic pegfilgrastim on day 2. Pathological complete response (pCR) was defined as absence of invasive disease in the breast and axilla. All patients underwent comprehensive BRACAnalysis®(Myriad). Results: For the 49 eligible patients median age was 50 years, median weight was 172 lbs, 18% were African American, and 37% had LN+ disease. 26% (13 /49) of patients carried deleterious BRCA mutation (9 BRCA 1, 4 BRCA 2). pCR of the cohort was 65%. Overall 61%, 96%, and 12 % patients demonstrated > Grade1 thrombocytopenia (Tp), anemia, or neutropenia, respectively; 4%, 6%, and 6% patients demonstrated grade 3/4 thrombocytopenia, anemia, or neutropenia, respectively. There was no association between pCR and anemia or neutropenia. Carboplatin dose reductions/delays/omission was more common in patients with Tp compared to patients without Tp (33% vs. 5%; p=0.02). Patients with Tp were more likely to achieve a pCR compared to patients without Tp (85% vs. 47%; p=0.013). 77% of BRCA carriers and 64% of BRCA wild type TNBC demonstrated Tp (NS). pCR rates in BRCA wild type patients with and without Tp were 82% and 47%, respectively (p=0.041). pCR rates in BRCA mutation carriers with and without Tp were 89% and 50%, respectively (p=0.20). On multivariable platelet count was independently associated with pCR (p=0.001)Conclusions: Tp was associated with decreased dose delivery of carboplatin but an improved pCR in BRCA wild type TNBC. Comprehensive assessment of HR defects beyond germline BRCA mutation status may be required to elucidate the biological process that explains this observation. Tp may be a harbinger of underlying HR deficiency and further correlative studies exploring this association of Tp with pathological response to carboplatin in TNBC are warranted. Citation Format: Priyanka Sharma, Benjamin C Powers, Bruce F Kimler, Claire Ward, Jennifer R Klemp, Carol S Connor, Marilee K McGinness, Joshua MV Mammen, Jamie L Wagner, Qamar J Khan, Roy A Jensen, Andrew K Godwin, Carol J Fabian. Thrombocytopenia is associated with pathological complete response to neoadjuvant carboplatin/docetaxel chemotherapy in BRCA wild type triple negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-16.

Pathological Response and Survival in Triple-Negative Breast Cancer Following Neoadjuvant Carboplatin plus Docetaxel

Purpose: Prognostic value of pathologic complete response (pCR) and extent of pathologic response attained with anthracycline-free platinum plus taxane neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) is unknown. We report recurrence-free survival (RFS) and overall survival (OS) according to degree of pathologic response in patients treated with carboplatin plus docetaxel NAC. Patients and Methods: One-hundred and ninety patients with stage I–III TNBC were treated with neoadjuvant carboplatin (AUC6) plus docetaxel (75 mg/m2) every 21 days × 6 cycles. pCR (no evidence of invasive tumor in breast and axilla) and Residual cancer burden (RCB) were evaluated. Patients were followed for recurrence and survival. Extent of pathologic response was associated with RFS and OS using the Kaplan–Meier method. Results: Median age was 51 years, and 52% were node-positive. pCR and RCB I rates were 55% and 13%, respectively. Five percent of pCR patients, 0% of RCB I patients, and 58% of RCB II/III patients received adjuvant anthracyclines. Three-year RFS and OS were 79% and 87%, respectively. Three-year RFS was 90% in patients with pCR and 66% in those without pCR [HR = 0.30; 95% confidence interval (CI), 0.14–0.62; P = 0.0001]. Three-year OS was 94% in patients with pCR and 79% in those without pCR (HR = 0.25; 95% CI, 0.10–0.63; P = 0.001). Patients with RCB I demonstrated 3-year RFS (93%) and OS (100%) similar to those with pCR. On multivariable analysis, higher tumor stage, node positivity, and RCB II/III were associated with worse RFS. Conclusions: Neoadjuvant carboplatin plus docetaxel yields encouraging efficacy in TNBC. Patients achieving pCR or RCB I with this regimen demonstrate excellent 3-year RFS and OS without adjuvant anthracycline.

Subcutaneous implant-based breast reconstruction, a modern challenge in postmastectomy radiation planning

PURPOSE A growing trend in breast reconstruction has been placement of tissue expanders in the pre pectoral space. This is a change from the practice of placement under the pectoralis major with or without an acellular dermal matrix (ADM) sling. The move toward pre pectoral placement with an ADM wrap has the intent of decreasing post-operative pain and decreasing animation deformities. The cosmesis of pre pectoral reconstructions in the setting of post mastectomy radiation has also appeared improved in our early experience, when compared to submuscular reconstructions. We sought to review the risks and benefits of this technique in the setting of post mastectomy radiation. METHODS AND MATERIALS Cases of ADM wrapped prepectoral tissue expander breast reconstructions in patients needing postmastectomy radiation therapy were reviewed in a single institution. RESULTS Thirty patients were treated with ADM wrapped prepectoral tissue expanders. On review of radiation plans, there were patients with anatomical variations, for whom standard dosimetric criteria were not met with partially wide tangent fields. Use of a medial electron field matched to steep photon tangents was not advised due to undercoverage of the tumor bed related to implant placement. Boost treatment was also omitted as a result of concerns regarding the implant location. CONCLUSIONS While new advances in plastic surgery may improve on cosmetic outcomes for breast cancer patients, increased discussion with radiation oncologists is needed to appropriately select candidates for these procedures. Prospective trials are necessary to ensure that these new techniques do not compromise oncologic outcomes.

Have We Come as Far as We Had Hoped? Discrimination in the Residency Interview

OBJECTIVE The primary objective was to use a pilot survey of fourth-year medical students at our institution to determine if female residency applicants were asked potentially illegal questions regarding family status and childbearing more frequently than male applicants. Secondary objectives included comparing the use of potentially illegal questions in surgical versus nonsurgical specialties and between community and academic residency programs. DESIGN A 20-item questionnaire was distributed to all fourth-year medical students at the University of Kansas School of Medicine. Data were analyzed in SPSS using descriptive statistics, bivariate analysis, and multivariate analysis. SETTING University of Kansas Health System, Tertiary Care Center. PARTICIPANTS Fourth-year medical students from the University of Kansas School of Medicine. RESULTS There were 57 survey respondents (51% male and 49% female). Female applicants were more likely to report being asked about their desire to have a family than male applicants (32% vs. 3%, respectively, p = 0.041). However, male and female students were equally likely to report being asked specifically if they had or intended to have children (p = 0.194). No significant differences were found in potentially illegal question-asking between surgical and nonsurgical specialties or between community-based and academic programs. CONCLUSIONS Although women now represent 47% of the applicant pool, gender discrimination in the residency interview has not been eradicated. Women are more likely to report potentially illegal questions regarding their desire to have a family on residency interviews than men. Community and academic programs appear to ask similar numbers and types of potentially illegal questions. Further study is warranted to determine if these findings apply to the entire applicant pool. Further education of interviewers is necessary regarding potentially illegal questions during the residency interview process.

Reply to letter: "waiting time for breast cancer treatment"

Reply: T he letter from Dr Fujita highlights an important component of the breast cancer workup that should be considered when assessing time to surgery. Lymphovascular invasion and tumor size have previously been shown to be predictors for axillary nodal metastasis in breast cancer.1–3 This supports our findings for the 24% of patients with nodal metastasis. The histomorphologic infiltrating pattern of invasive lobular carcinoma contributes to lower sensitivity of ultrasonographic detection of position axillary lymph nodes. A similar reduction in ultrasound identification sensitivity is also seen with micrometastic lymph nodes.4,5 These ultrasonographic limitations may have contributed to the 24% of patients who were clinically nodenegative then determined to be pathologically node-positive at surgery. As stated by Fujita, magnetic resonance imaging and positron emission tomographic scan are equal or infe-