In the neoadjuvant GeparSixto study, adding carboplatin to taxane- and anthracycline-based chemotherapy improved pathological complete response (pCR) rates in patients with triple-negative breast ...cancer (TNBC). Here, we present survival data and the potential prognostic and predictive role of homologous recombination deficiency (HRD).
Patients were randomized to paclitaxel plus nonpegylated liposomal doxorubicin (Myocet®) (PM) or PM plus carboplatin (PMCb). The secondary study end points disease-free survival (DFS) and overall survival (OS) were analyzed. Median follow-up was 47.3 months. HRD was among the exploratory analyses in GeparSixto and was successfully measured in formalin-fixed, paraffin-embedded tumor samples of 193/315 (61.3%) participants with TNBC. Homologous recombination (HR) deficiency was defined as HRD score ≥42 and/or presence of tumor BRCA mutations (tmBRCA).
A significantly better DFS (hazard ratio 0.56, 95% CI 0.34–0.93; P = 0.022) was observed in patients with TNBC when treated with PMCb. The improvement of OS with PMCb was not statistically significant. Additional carboplatin did not improve DFS or OS in patients with HER2-positive tumors. HR deficiency was detected in 136 (70.5%) of 193 triple-negative tumors, of which 82 (60.3%) showed high HRD score without tmBRCA. HR deficiency independently predicted pCR (ypT0 ypN0) odds ratio (OR) 2.60, 95% CI 1.26–5.37, P = 0.008. Adding carboplatin to PM significantly increased the pCR rate from 33.9% to 63.5% in HR deficient tumors (P = 0.001), but only marginally in HR nondeficient tumors (from 20.0% to 29.6%, P = 0.540; test for interaction P = 0.327). pCR rates with carboplatin were also higher (63.2%) than without carboplatin (31.7%; OR 3.69, 1.46–9.37, P = 0.005) in patients with high HRD score but no tmBRCA. DFS rates were improved with addition of carboplatin, both in HR nondeficient (hazard ratio 0.44, 0.17–1.17, P = 0.086) and HR deficient tumors (hazard ratio 0.49, 0.23–1.04, P = 0.059).
The addition of carboplatin to neoadjuvant PM improved DFS significantly in TNBC. Long-term survival analyses support the neoadjuvant use of carboplatin in TNBC. HR deficiency in TNBC and HRD score in non-tmBRCA TNBC are predictors of response. HRD does not predict for carboplatin benefit.
The neoadjuvant phase III GeparSepto study showed that substituting nab-paclitaxel for standard solvent-based paclitaxel significantly improved the pathologic complete response (pCR) rate achieved ...with a sequential neoadjuvant chemotherapy regimen of paclitaxel, epirubicin, and cyclophosphamide for high-risk primary breast cancer. Recent trials demonstrated that in HER2+ breast cancer pCR can be increased by using pertuzumab in addition to trastuzumab and chemotherapy. The present analysis focuses on efficacy and safety data from the subset of patients with HER2+ tumors from the GeparSepto trial (n = 396) in comparison to the HER2- cohort.
Patients with histologically confirmed breast cancer (n = 1206) received four cycles of weekly paclitaxel either solvent-based (Pac) or nab-paclitaxel (nab-Pac), according to randomization followed by 4 cycles of epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 q3w, with concurrent trastuzumab and pertuzumab q3w for those with HER2+ tumors. The primary endpoint was pCR defined as ypT0 ypN0.
Higher rates of pCR were achieved in HER2+ than in HER2- tumors (57.8% versus 22.0%,P < 0.0001), with the highest rate in the HER2+/HR- cohort (71.0%; 66.7% Pac, 74.6% nab-Pac). In HER2+/HR+ tumors, the pCR rate was 52.9% (49.7% Pac, 56.4% nab-Pac). Grade ≥3 toxic effects were significantly more common in HER2+ than in HER2- patients, with grade 3–4 diarrhea in 7.6% versus 0.9% (P < 0.001) and febrile neutropenia in 6.3% versus 3.3% (P = 0.023) of patients. Left ventricular ejection fraction decreases from baseline were uncommon, with 2.0% versus 0.4% of patients showing decreases to <50% along with a ≥10% decrease from baseline.
In HER2+ early breast cancer, a dual HER2-targeted combination of pertuzumab and trastuzumab, together with taxane–epirubicin–cyclophosphamide neoadjuvant chemotherapy, achieved high rates of pCR.
Abstract The eLEcTRA trial compared efficacy and safety of letrozole combined with trastuzumab to letrozole alone in patients with HER2 and hormone receptor (HR) positive metastatic breast cancer ...(MBC). Patients were randomized to either letrozole alone (arm A, n = 31) or letrozole plus trastuzumab (arm B, n = 26) as first-line treatment. Additional 35 patients with HER2 negative and HR positive tumors received letrozole alone (arm C). Median time to progression in arm A was 3.3 months compared to 14.1 months in arm B (hazard ratio 0.67; p = 0.23) and 15.2 months in arm C (hazard ratio 0.71; p = 0.03). Clinical benefit rate was 39% for arm A compared to 65% in arm B (odds ratio 2.99, 95% CI 1.01–8.84) and 77% in arm C (odds ratio 5.34, 95% CI 1.83–15.58). The eLEcTRA trial showed that the combination of letrozole and trastuzumab is a safe and effective treatment option for patients with HER2 positive and HR positive MBC.
Background
Acellular dermal matrix is increasingly used as caudolateral coverage for breast implants in immediate breast reconstruction after skin-sparing mastectomy or in the correction of ...implant-associated breast deformities. Matrices of human, bovine, and porcine origin are available. The purpose of this retrospective multicenter study was to report experiences with porcine acellular dermal matrices, as only limited data can be found in the literature.
Methods
In the hospital databases of five institutions, 127 patients were identified who underwent breast reconstructions in 156 breasts using an acellular porcine dermal matrix. Medical records were reviewed. Patients were divided into three groups: immediate expander-implant or direct to implant reconstructions (
n
= 98), delayed expander-implant reconstructions (
n
= 14), and revision surgery for implant-associated breast deformities (
n
= 44).
Results
With a mean follow-up of 19.6 months, total major complication rate was 7.1 %: implant loss (3.2 %), skin flap necrosis (2.6 %), delayed skin healing (2.6 %), hematoma (1.9 %), seroma (1.3 %), infection (0.6 %), and capsular contracture (0.6 %). Total minor complication rate was 22.9 %, with seroma being the most frequent complication (19.2 %). In the group of immediate breast reconstructions, 20.4 % of the breasts had received radiotherapy in the past. These patients exhibited a significantly higher rate of seroma than patients without prior radiotherapy (35.0 vs. 14.9 %,
p
= 0.031).
Conclusions
Complication rates using porcine acellular dermal matrix in breast reconstruction are comparable to complication rates reported in studies using human acellular dermal matrices. Thus, porcine acellular dermal matrices can safely be applied in breast reconstructive surgery.
Abstract Background Patients with invasive residual disease after neoadjuvant chemotherapy (NACT) are considered to have chemo-resistant breast cancer. Bisphosphonates are an established treatment ...for bone metastases and are of potential benefit as adjuvant treatment in early breast cancer. Patients and methods Patients who had invasive tumour residuals (ypT1-4 and/or ypN+) after a minimum of four cycles of anthracycline-taxane-containing NACT were eligible for the NeoAdjuvant Trial Add-oN study. Patients were randomised within 3 years after surgery to receive zoledronate 4 mg i.v. for 5 years versus observation. Zoledronate was given every 4 weeks for the first 6 months, every 3 months for the following 2 years, and every 6 months for the last 2.5 years. Primary objective was disease-free survival. Results After a median time of 54.7 months no difference in disease-free survival was observed between the zoledronate and observation groups (hazard ratio HR 0.960, 95% confidence interval CI 0.709–1.30, log rank P = 0.789). Various subgroups were examined without identifying a treatment effect of zoledronate. Patients over 55 years of age showed a HR of 0.832 in favour of zoledronate, but the result was not significant ( P = 0.480). A similar result was obtained for overall survival with a HR of 1.19 (95% CI 0.79–1.79; log rank P = 0.408). Zoledronate was well tolerated and no new toxicity signal was identified. Conclusion Postneoadjuvant treatment with zoledronate does not improve outcome in patients without pathological complete response after neoadjuvant anthracycline-taxane-based chemotherapy for early breast cancer.
Summary Background A randomized, double-blind, multicenter study was conducted to compare the anti-tumor activity of letrozole vs. tamoxifen in postmenopausal women with ER and/or PgR positive ...primary untreated breast cancer Patients and methods Three hundred thirty-seven postmenopausal women with ER and/or PgR positive primary untreated breast cancer were randomly assigned once daily treatment with either letrozole 2 5 mg or tamoxifen 20 mg for four months At baseline none of the patients were considered to be candidates for breast-conserving surgery (BCS) and 14% of the patients were considered inoperable The primary endpoint was to compare overall objective response (CR + PR) determined by clinical palpation Secondary endpoints included overall objective response on ultrasound and mammography and the number of patients who qualified for BCS Results Overall objective response rate (clinical palpation) was statistically significantly superior in the letrozole group, 55% compared to tamoxifen, 36% (P < 0 001) Secondary endpoints of ultrasound response, 35% vs 25% (P = 0.042), mammographic response, 34% vs 16% (P < 0 001), and BCS. 45% vs. 35% (P = 0 022) between the letrozole and tamoxifen groups, respectively, showed letrozole to be significantly superior Both treatments were well tolerated Conclusions This study shows that letrozole is more effective than tamoxifen as preoperative therapy in postmenopausal patients with ER and/or PgR positive primary untreated breast cancer and is at least as well tolerated
Purpose
Postoperative seromas are a problem in the surgical treatment of breast cancer. The aim of the study was to evaluate whether the lysine-urethane-based tissue adhesive TissuGlu
®
without ...drainage is equal/ non-inferior to standard mastecomy with drainage.
Methods
The study was designed as a prospective, randomized, multicentre non-inferiority study comparing the use of TissuGlu
®
without drainage with standard wound care with a drain insertion in ablative breast procedures. The number of clinical interventions, quality of life and wound complications were followed-up for 90 days in both groups.
Results
Although the statistical power was not reached, twice as many clinical interventions were performed in the TissuGlu
®
group than in the drainage group, especially aspirations of clinically relevant seromas (
p
= 0.014). The TissuGlu
®
group produced overall less wound fluid, but developed a clinically relevant seroma (100% vs. 63%) which made an intervention necessary. Less hospitalisation time was observed in the TissuGlu
®
group, but the complication rate was higher. There was no significant difference in regards to postoperative pain. In summary the non-inferiority of TissuGlu
®
compared to standard drainage couldn’t be reached.
Discussion
The present evaluation shows no advantage of the tissue adhesive TissuGlu
®
in terms of seroma formation and frequency of intervention compared to a standard drainage for mastectomies, but the shorter inpatient stay certainly has a positive effect on the quality of life.
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