7 research outputs found
Abstract P1-13-10: Adjuvant treatment of HER2+ breast cancer: Should trastuzumab be given sequentially or concurrently with chemotherapy?
No full textAbstract
Background
Human Epidermal growth factor Receptor 2 positive (HER2+) breast cancers have a high risk of recurrence in the absence of systemic treatment. The monoclonal antibody trastuzumab in combination with chemotherapy has significantly improved survival. Randomized trials have given trastuzumab both concurrently and sequentially with chemotherapy. To date, only one study reported a comparison between concurrent and sequential trastuzumab, with a numerically but not statistically significant benefit for concurrent use.
Our aim is to evaluate whether there is a difference in survival between patients who received trastuzumab sequentially to chemotherapy compared to concurrently with chemotherapy using data from the population-based, Netherlands Cancer Registry (NCR).
Methods
All women diagnosed in the Netherlands with a HER2+, TanyNanyM0 breast tumor between 2005 and 2007 who received both chemotherapy and trastuzumab were identified from the NCR.
Kaplan Meier survival estimates and Cox regression were used to compare recurrence free survival (RFS) and overall survival (OS) by trastuzumab sequence. Hazard ratios (HR) were adjusted for grade, pathological T-stage, pathological N-stage, estrogen receptor (ER), progesterone receptor, radiotherapy, hormonal therapy and ovarian ablation.
Results
A total of 1,849 patients were identified, with a mean follow-up of 7.8 years. Of these, 1,260 received concurrent trastuzumab and 589 sequential trastuzumab. Most tumors were grade 3, node positive and ER+. During follow-up 358 RFS events occurred, 231 in the concurrently treated patients compared to 127 in sequentially treated patients. Regarding OS, 290 deaths were observed, 188 deaths in concurrently treated patients compared to 102 deaths in sequentially treated patients, respectively.
OS and RFS were similar among sequentially versus concurrently treated patients (adjusted HR 1.11; 95% CI 0.87-1.42; P=0.420 and adjusted HR 1.15; 95% CI 0.92-1.44; P=0.209, respectively).
Conclusion
We observed no significant difference in OS and RFS between patients who received sequential trastuzumab compared to patients treated concurrently. Based on our results no recommendation can be made favoring either of the two treatment sequences for the adjuvant treatment of HER2+ breast cancer patients.
Citation Format: Dackus GMHE, Jóźwiak K, Van der Wall E, Van Diest PJ, Hauptmann M, Siesling S, Sonke GS, Linn SC. Adjuvant treatment of HER2+ breast cancer: Should trastuzumab be given sequentially or concurrently with chemotherapy? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-13-10.</jats:p
Abstract P2-09-16: How population-based data complement trial data in the adjuvant endocrine treatment of ER+/HER2+ breast cancers
No full textAbstract
Background
This study is part of the Netherlands Breast Cancer Project, initiated to address research questions that are unlikely answered by future randomized controlled trials (RCT). Here we investigated whether aromatase inhibitors (AI) are superior over tamoxifen (TAM), in the treatment of Estrogen Receptor (ER) positive Human Epidermal growth factor Receptor 2 (HER2) positive breast cancer, using treatment and outcome data from the population based Netherlands Cancer Registry (NCR). RCTs showed superiority of AI over TAM in postmenopausal ER+/HER2+ patients while a (non-significant) suggestion for worse outcome was observed among premenopausal patients treated with AI in the SOFT/TEXT trial. Perimenopausal women were not considered in these trials.
Methods
Dutch women without a prior malignancy, diagnosed between 2005-2007 with an ER+/HER2+, endocrine treated, non-metastatic, invasive breast cancer, were identified through the NCR and followed until 2013. Since data on menopausal status were lacking, we used age at diagnosis as a proxy to categorize patients as premenopausal (≤45 years), perimenopausal (45-55 years) and postmenopausal (&gt;55 years). A time-dependent variable was calculated indicating whether AI treatment was given for &gt;50% (denoted AI treated) vs. &lt;50% (denoted TAM treated) of endocrine treatment duration. Recurrence-free survival (RFS) and overall survival (OS) were assessed using an extended Kaplan-Meier survival estimator and Cox proportional hazards regression. Hazard Ratios (HR) for the TAM/AI comparison, were adjusted for chemotherapy, trastuzumab, age at diagnosis, lymph node status, grade, clinical T stage, and ovarian ablation.
Results
We included 1158 patients: 326 pre-, 306 peri- and 526 postmenopausal. Of these, 229 received TAM and 929 AI. During follow-up, 239 RFS and 184 OS events were observed. In the TAM treated group, 56 RFS and 45 OS events were observed, in the AI treated group 183 RFS and 139 RFS events were observed respectively.
No differences in RFS were observed comparing AI to TAM treated patients in the premenopausal (HR 1.33; 95% CI 0.71-2.49; P=0.378) and postmenopausal (HR 0.84, 95%CI 0.54-1.32; P=0.456) group. However, perimenopausal patients benefitted significantly from AI compared with TAM (HR 0.50; 95% CI 0.27-0.95). Results were similar for OS: no significant benefit from AI when compared to TAM in pre- (HR 1.41; 95% CI 0.62-3.19; P=0.408) and postmenopausal (HR 0.75; 95% CI 0.47-1.22; P=0.245) patients while perimenopausal patients derived significant benefit from AI treatment (HR 0.42; 95% CI 0.20-0.85; P=0.016).
Conclusion
In this population based cohort study we observed superiority for AI over TAM in the treatment of ER+/HER2+ perimenopausal patients. Data were suggestive in favor of AI when compared to TAM for postmenopausal patients while an indication of worse outcome with AI was seen in premenopausal patients, consistent with results of the SOFT/TEXT trial. Although we used age as a proxy for menopausal status, our results are consistent with previous RCTs. Population based data may therefore provide a reliable source of information when new RCTs might not be feasible anymore.
Citation Format: Dackus GMHE, Jozwiak K, Sonke GS, Van der Wall E, Van Diest PJ, Hauptmann M, Siesling S, Linn SC. How population-based data complement trial data in the adjuvant endocrine treatment of ER+/HER2+ breast cancers [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-09-16.</jats:p
Abstract PD5-02: The effect of trastuzumab-based therapy on overall survival in small, node-negative HER2-positive breast cancer: To treat or not to treat?
No full textAbstract S6-06: The effect of trastuzumab-based therapy on overall survival in small, node-negative HER2-positive breast cancer: To treat or not to treat?
No full textAbstract OT1-03-10: A phase I followed by a randomized phase II trial of two cycles carboplatin-olaparib followed by olaparib monotherapy versus capecitabine in BRCA-1 or -2 mutated Her2 negative advanced breast cancer as first line treatment (REVIVAL study)
No full textAbstract P5-08-07: The long-term prognosis of breast cancers patients diagnosed ≤40 years in the absence of adjuvant systemic therapy
No full textAbstract
This abstract was withdrawn by the authors.</jats:p
Prognostic Value of Stromal Tumor-Infiltrating Lymphocytes in Young, Node-Negative, Triple-Negative Breast Cancer Patients Who Did Not Receive (neo)Adjuvant Systemic Therapy
No full textPURPOSE: Triple-negative breast cancer (TNBC) is considered aggressive, and therefore, virtually all young patients with TNBC receive (neo)adjuvant chemotherapy. Increased stromal tumor-infiltrating lymphocytes (sTILs) have been associated with a favorable prognosis in TNBC. However, whether this association holds for patients who are node-negative (N0), young (< 40 years), and chemotherapy-naïve, and thus can be used for chemotherapy de-escalation strategies, is unknown. METHODS: We selected all patients with N0 TNBC diagnosed between 1989 and 2000 from a Dutch population-based registry. Patients were age < 40 years at diagnosis and had not received (neo)adjuvant systemic therapy, as was standard practice at the time. Formalin-fixed paraffin-embedded blocks were retrieved (PALGA: Dutch Pathology Registry), and a pathology review including sTILs was performed. Patients were categorized according to sTILs (< 30%, 30%-75%, and ≥ 75%). Multivariable Cox regression was performed for overall survival, with or without sTILs as a covariate. Cumulative incidence of distant metastasis or death was analyzed in a competing risk model, with second primary tumors as competing risk. RESULTS: sTILs were scored for 441 patients. High sTILs (≥ 75%; 21%) translated into an excellent prognosis with a 15-year cumulative incidence of a distant metastasis or death of only 2.1% (95% CI, 0 to 5.0), whereas low sTILs (< 30%; 52%) had an unfavorable prognosis with a 15-year cumulative incidence of a distant metastasis or death of 38.4% (32.1 to 44.6). In addition, every 10% increment of sTILs decreased the risk of death by 19% (adjusted hazard ratio: 0.81; 95% CI, 0.76 to 0.87), which are an independent predictor adding prognostic information to standard clinicopathologic variables (χ2 = 46.7, P < .001). CONCLUSION: Chemotherapy-naïve, young patients with N0 TNBC with high sTILs (≥ 75%) have an excellent long-term prognosis. Therefore, sTILs should be considered for prospective clinical trials investigating (neo)adjuvant chemotherapy de-escalation strategies
