Purpose
Neoadjuvant systemic treatment (NST) is increasingly administered in breast cancer patients. This study was conducted to identify predictors for tumor response in the breast and axilla.
...Methods
All female patients with nonmetastatic, noninflammatory breast cancer receiving NST between 2003‐2013 at the Catharina Cancer Institute in Eindhoven, The Netherlands, were included.
Results
The majority of 216 of the 337 patients receiving NST (65%) presented with a cT2 tumor. In 159 patients (47%), the axilla was clinically node positive. A pathologic complete response (pCR) in the breast was achieved in 83 patients (24.6%), and a pCR in the axilla in 65 node‐positive patients (40.9%). The triple‐negative (OR 4.29, 95% CI 2.15‐8.55) and hormone receptor (HR)‐negative/HER2‐positive tumors (OR 3.73, 95% CI 1.59‐8.75) were associated with in‐breast pCR. Patients with invasive lobular carcinoma (ILC) were less likely to experience in‐breast pCR (OR 0.10, 95% CI 0.01‐0.73) than those with invasive ductal cancer. Axillary pCR was found in 65 clinically node‐positive patients (41%). Axillary pCR was more likely to occur in HR‐positive/HER2‐positive (OR 6.24, 95% CI 1.86‐20.90) and HR‐negative/HER2‐positive tumors (OR 6.41, 95% CI 1.95‐21.06), compared to HER2‐negative disease. In‐breast pCR was strongly associated with axillary pCR (OR 10.89, 95% CI 4.20‐28.22).
Conclusion
Response to NST in the breast and axilla is largely determined by receptor status, with high pCR rates occurring in HER2‐positive and triple‐negative tumors. For axillary pCR, in‐breast pCR and HER2‐positive disease are the most important predictive factors.
The primary aim of treatment of a patient who has developed metastatic disease is palliation. The objectives of the current study are to describe and quantify the clinical management of women with ...metastatic breast cancer from the diagnosis of metastatic disease until death and to analyze differences between age groups.
Data were collected from the medical files of all patients (n = 116) who had died after December 31, 1999, after a diagnosis of metastatic breast cancer in two teaching hospitals in the south of the Netherlands.
Of the 116 patients included in our study, 10 (9%) already had metastatic disease at diagnosis and 106 developed distant disease after the diagnosis of localized breast cancer. Before they died, 70% of the 116 patients developed metastases in one or more bones, 50% in the lung and/or pleura, 50% in the abdominal viscera, 23% in the central nervous system, and 19% in the skin. Patients younger than 50 years were much more likely to develop metastases in the central nervous system than patients 50 years and older. Seventy-seven (66%) of the 116 patients with metastatic breast cancer received chemotherapy. This proportion decreased with age (p = 0.005), as did the number of schemes per patient. Together, they received 132 chemotherapy schemes, of which 35 (27%) resulted in partial remission or stabilization of the disease process. Ninety-eight patients (84%) received hormonal treatment. This proportion did not differ between the three age groups. Together, they received 216 hormonal treatments, 38 (16%) of which resulted in partial remission or stabilization of the disease process. Seventy-nine patients (68%) received palliative radiotherapy. This proportion decreased with age (p = 0.03). Together, they underwent 216 courses, 176 (77%) of which resulted in relief of the complaints.
Patients aged 70 years and older are less likely to receive chemotherapy or radiotherapy. Part of this difference could be explained by their shorter survival time after the diagnosis of metastatic disease and their lower risk of developing brain and bone metastases. However, more research is needed to understand the age-related differences in the treatment of metastatic breast cancer, and especially how comorbidity and frailty limit therapeutic choices.
Five percent of all patients with breast cancer have distant metastatic disease at initial presentation. Because metastatic breast cancer is considered to be an incurable disease, it is generally ...treated with a palliative intent. Recent non-randomized studies have demonstrated that (complete) resection of the primary tumor is associated with a significant improvement of the survival of patients with primary metastatic breast cancer. However, other studies have suggested that the claimed survival benefit by surgery may be caused by selection bias. Therefore, a randomized controlled trial will be performed to assess whether breast surgery in patients with primary distant metastatic breast cancer will improve the prognosis.
Randomization will take place after the diagnosis of primary distant metastatic breast cancer. Patients will either be randomized to up front surgery of the breast tumor followed by systemic therapy or to systemic therapy, followed by delayed local treatment of the breast tumor if clinically indicated.Patients with primary distant metastatic breast cancer, with no prior treatment of the breast cancer, who are 18 years or older and fit enough to undergo surgery and systemic therapy are eligible. Important exclusion criteria are: prior invasive breast cancer, surgical treatment or radiotherapy of this breast tumor before randomization, irresectable T4 tumor and synchronous bilateral breast cancer. The primary endpoint is 2-year survival. Quality of life and local tumor control are among the secondary endpoints.Based on the results of prior research it was calculated that 258 patients are needed in each treatment arm, assuming a power of 80%. Total accrual time is expected to take 60 months. An interim analysis will be performed to assess any clinically significant safety concerns and to determine whether there is evidence that up front surgery is clinically or statistically inferior to systemic therapy with respect to the primary endpoint.
The SUBMIT study is a randomized controlled trial that will provide evidence on whether or not surgery of the primary tumor in breast cancer patients with metastatic disease at initial presentation results in an improved survival.
NCT01392586.
Aromatase inhibitors (AIs) are given as adjuvant therapy for hormone receptor-positive breast cancer in postmenopausal women, also to those with chemotherapy-induced ovarian function failure. The ...current analysis reports on endocrine data of patients with chemotherapy-induced ovarian function failure who were included in the phase III DATA study assessing different durations of adjuvant anastrozole after tamoxifen.
We identified all patients with chemotherapy-induced ovarian function failure. Women who underwent a bilateral ovariectomy or used luteinizing hormone-releasing hormone agonists before random assignment were excluded. Plasma estradiol and follicle-stimulating hormone levels were monitored until 30 months after random assignment at local laboratories. We aimed to determine the ovarian function recovery (OFR) rate during AI use by the cumulative incidence competing risk method and analyzed the trend of estradiol levels during AI use by a nested case-control approach in which a subset of control subjects were compared with the OFR patients excluding the value at OFR diagnosis.
The 329 eligible patients had a median age of 50.0 years (range = 45-57 years) at random assignment. Thirty-nine patients developed OFR, corresponding with a 30-month recovery rate of 12.4%. Of these, 11 (28.2%) were age 50 years or older at AI initiation. The estradiol level decreased statistically significantly by 37.8% (95% CI = 27.4% to 46.7%) over the initial 30 months of AI treatment in both groups. However, the estradiol levels in the women who experienced OFR remained statistically significantly higher (difference = 20.6%, 95% CI = 2.0% to 42.7%) prior to OFR diagnosis compared with those who did not experience OFR.
The risk of OFR during AI treatment in breast cancer patients with chemotherapy-induced ovarian function failure is relevant, even beyond 45 years. Furthermore, women experiencing OFR had statistically significant higher estradiol levels during AI treatment (before OFR) than those without, with potential consequences regarding efficacy.
To analyze recurrence patterns in patients with cancer of the esophagus or gastroesophageal junction treated with either preoperative chemoradiotherapy (CRT) plus surgery or surgery alone.
Recurrence ...pattern was analyzed in patients from the previously published CROSS I and II trials in relation to radiation target volumes. CRT consisted of five weekly courses of paclitaxel and carboplatin combined with a concurrent radiation dose of 41.4 Gy in 1.8-Gy fractions to the tumor and pathologic lymph nodes with margin.
Of the 422 patients included from 2001 to 2008, 418 were available for analysis. Histology was mostly adenocarcinoma (75%). Of the 374 patients who underwent resection, 86% were allocated to surgery and 92% to CRT plus surgery. On January 1, 2011, after a minimum follow-up of 24 months (median, 45 months), the overall recurrence rate in the surgery arm was 58% versus 35% in the CRT plus surgery arm. Preoperative CRT reduced locoregional recurrence (LRR) from 34% to 14% (P < .001) and peritoneal carcinomatosis from 14% to 4% (P < .001). There was a small but significant effect on hematogenous dissemination in favor of the CRT group (35% v 29%; P = .025). LRR occurred in 5% within the target volume, in 2% in the margins, and in 6% outside the radiation target volume. In 1%, the exact site in relation to the target volume was unclear. Only 1% had an isolated infield recurrence after CRT plus surgery.
Preoperative CRT in patients with esophageal cancer reduced LRR and peritoneal carcinomatosis. Recurrence within the radiation target volume occurred in only 5%, mostly combined with outfield failures.
The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD).
...Guidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer. OMEC identified patients for whom the term OMD is considered or could be considered. Disease-free interval (DFI) was defined as the time between primary tumor treatment and detection of OMD.
Moderate to high quality of evidence was found (i.e. 1 randomized and 4 non-randomized phase II trials) resulting in moderate recommendations. OMD is considered in esophagogastric cancer patients with 1 organ with ≤ 3 metastases or 1 involved extra-regional lymph node station. In addition, OMD continues to be considered in patients with OMD without progression in number of metastases after systemic therapy. 18F-FDG PET/CT imaging is recommended for baseline staging and for restaging after systemic therapy when local treatment is considered. For patients with synchronous OMD or metachronous OMD and a DFI ≤ 2 years, recommended treatment consists of systemic therapy followed by restaging to assess suitability for local treatment. For patients with metachronous OMD and DFI > 2 years, upfront local treatment is additionally recommended.
These multidisciplinary European clinical practice guidelines for the uniform definition, diagnosis and treatment of esophagogastric OMD can be used to standardize inclusion criteria in future clinical trials and to reduce variation in treatment.
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•Multidisciplinary European clinical practice guidelines were developed.•One organ with ≤ 3 metastases is considered OMD.•One extra-regional lymph node station is considered OMD.•Patients with OMD undergo systemic therapy followed by restaging.•Patients without progression at 18F-FDG PET/CT restaging undergo local treatment.
Invasive lobular breast cancer (ILC) is less common than invasive ductal breast cancer (IDC) and appears to have a distinct biology. Inconsistent findings regarding disease-free survival (DFS) are ...probably due to the fact that histologic type is related to hormone receptor status. This study aims to determine whether the type of the primary breast cancer histology is an independent prognostic factor for DFS, the risk pattern of loco-regional recurrences and distant metastases (DM), and whether it is a prognostic factor for the site of DM. All Dutch women diagnosed between 2003 and 2005 with ILC (
n
= 2,949) or IDC (
n
= 22,378) were selected from the Netherlands Cancer Registry. DFS was assessed using proportional hazard regression analysis. Compared to patients with IDC, those with ILC were significantly older and more likely to have more than three positive lymph nodes and have larger, better differentiated, more multifocal, and hormone receptor positive tumors (all
P
< 0.001). ILC was more likely to metastasize to the gastrointestinal organs and bones and less likely to the lung, central nervous system, and lymph nodes. Within the ER+PR+ and ER+PR− subgroups ILC was still more likely to metastasize to gastrointestinal organs and less likely to the lung. The timing of recurrence was correlated to hormone receptor status, independent of histological type. Highest risks were observed among ER−PR− patients within 2 years of surgery. Multivariable analysis showed that histological type is not an independent significant prognostic factor of DFS for the first 3 years post-surgery and thereafter (<3 years HR 0.91, 95 % CI 0.78–1.06, >3 years HR 1.07, 95 % CI 0.88–1.30). Histological type should not be considered an important prognostic factor for the risk and risk pattern of recurrences.
Approximately 15% to 43% of esophageal adenocarcinomas (EACs) are human epidermal growth factor receptor 2 (HER2) positive. Because dual-agent HER2 blockade demonstrated a survival benefit in breast ...cancer, we conducted a phase II feasibility study of trastuzumab and pertuzumab added to neoadjuvant chemoradiotherapy (nCRT) in patients with EAC.
Patients with resectable HER2-positive EAC received standard nCRT with carboplatin and paclitaxel and 41.4 Gy of radiotherapy, with 4 mg/kg of trastuzumab on day 1, 2 mg/kg per week during weeks 2 to 6, and 6 mg/kg per week during weeks 7, 10, and 13 and 840 mg of pertuzumab every 3 weeks. The primary end point was feasibility, defined as ≥ 80% completion of treatment with both trastuzumab and pertuzumab. An exploratory comparison of survival with a propensity score-matched cohort receiving standard nCRT was performed, as were exploratory pharmacokinetic and biomarker analyses.
Of the 40 enrolled patients (78% men; median age, 63 years), 33 (83%) completed treatment with trastuzumab and pertuzumab. No unexpected safety events were observed. R0 resection was achieved in all patients undergoing surgery, with pathologic complete response in 13 patients (34%). Three-year progression-free and overall survival (OS) were 57% and 71%, respectively (median follow-up, 32.1 months). Compared with the propensity score-matched cohort, a significantly longer OS was observed with HER2 blockade (hazard ratio, 0.58; 95% CI, 0.34 to 0.97). Results of pharmacokinetic analysis and activity on
Ffluorodeoxyglucose positron emission tomography scans did not correlate with survival or pathologic response. Patients with HER2 3+ overexpression or growth factor receptor-bound protein 7 (Grb7) -positive tumors at baseline demonstrated significantly better survival (
= .007) or treatment response (
= .016), respectively.
Addition of trastuzumab and pertuzumab to nCRT in patients with HER2-positive EAC is feasible and demonstrates potentially promising activity compared with historical controls. HER2 3+ overexpression and Grb7 positivity are potentially predictive for survival and treatment response, respectively.
Purpose
The phase III DATA study compared 6 and 3 years of adjuvant anastrozole following 2–3 years of tamoxifen in postmenopausal breast cancer patients. This pre-planned side-study assessed the ...relationship between a reduced bone mineral density (BMD) and distant recurrence-free survival (DRFS), and evaluated the effect of bisphosphonates on DRFS.
Methods
We selected all patients with a BMD measurement within 3 years after randomisation (landmark) without any DRFS events. Kaplan–Meier methods and Cox proportional hazards models were used for analyses.
Results
Of 1860 eligible patients, 1142 had a DEXA scan before the landmark. The BMD was normal in 436 (38.2%) and showed osteopenia in 565 (49.5%) and osteoporosis in 141 (12.3%) patients. After a median follow-up of 5.0 years from the landmark, neither osteopenia nor osteoporosis (compared with normal BMD) were associated with DRFS in both the 6-year osteopenia HR 0.82 (95% CI 0.45–1.49), osteoporosis HR 1.10 (95% CI 0.26–4.67) and the 3-year arm osteopenia HR 0.75 (95% CI 0.40–1.42), osteoporosis HR 1.86 (95% CI 0.43–8.01). Moreover, bisphosphonate use did not impact DRFS.
Conclusion
No association was observed between a reduced BMD and DRFS. Neither did we observe an impact of bisphosphonates on DRFS.
Abstract Purpose Patients with chemotherapy-induced ovarian function failure (CIOFF) may experience ovarian function recovery (OFR). Earlier, we showed that OFR during treatment with anastrozole ...impacted the prognosis of hormone receptor-positive (HR+) breast cancer (BC) patients with CIOFF. Here, we present the long-term follow-up results. Methods Postmenopausal women with HR+ BC who were 45–57 years of age and received chemotherapy were identified from the phase 3 DATA study (NCT00301457) on the extended use of anastrozole. Eligible patients were categorised into two groups: patients with CIOFF and definitely postmenopausal patients. Patients with CIOFF were monitored for OFR. Disease-free survival (DFS), distant recurrence-free survival (DRFS), and overall survival (OS) were compared between patients with OFR and patients without OFR using multivariable Cox regression analyses, including OFR as a time-dependent covariate. BC-specific mortality (BCSM) was compared between groups using the Fine and Gray method. Results This study included 656 patients: 395 patients with CIOFF and 261 definitely postmenopausal patients. OFR occurred in 39 (12%) of 329 patients with CIOFF who were monitored for OFR. The median follow-up time was 13.3 years. Patients with OFR experienced a deterioration in DFS (hazard ratio (HR) = 1.54; 95% confidence interval (CI) 0.85–2.81), DRFS (HR = 1.51; 95% CI 0.73–3.11), OS (HR = 1.64; 95% CI 0.75–3.55), and BCSM (subdistribution HR = 1.98; 95% CI 0.84–4.63) when compared with patients without OFR. Conclusion In patients with CIOFF, OFR during treatment with anastrozole was associated with a deterioration in BC outcomes. These findings underscore the importance of adequate ovarian function suppression in this subgroup of patients.
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