Neoadjuvant versus adjuvant chemotherapy in premenopausal patients with tumours considered too large for breast conserving surgery: Preliminary results of a randomised trial: S6

doi:10.1016/0959-8049(94)90537-1

European Journal of Cancer

Volume 30, Issue 5, 1994, Pages 645-652

https://doi.org/10.1016/0959-8049(94)90537-1 Get rights and content

Abstract

The aim of this study was to assess a potential advantage in survival by neoadjuvant as compared to adjuvant chemotherapy. 414 premenopausal patients with T2-T3 N0-N1 M0 breast cancer were randomised to receive either four cycles of neoadjuvant chemotherapy (cyclophosphamide, doxorubicin, 5-fluorouracil), followed by local-regional treatment (group I) or four cycles of adjuvant chemotherapy after primary irradiation ± surgery (group II). Surgery was limited to those patients with a persisting mass after irradiation, and aimed to be as conservative as possible. 390 patients were evaluable. With a median follow-up of 54 months, we observed a statistically significant difference (P = 0.039) in survival in favour of the neoadjuvant chemotherapy group. A similar trend was seen when the time to metastatic recurrence was evaluated (P = 0.09). At this stage, no difference in disease-free interval or local recurrence between these two groups could be observed. The mean total dose of chemotherapy administered was similar in both groups. On average, group I had more intensive chemotherapy regimes (doxorubicin P = 0.02) but fewer treatment courses (P = 0.008) as compared to the treated patients in group II. Haematological tolerance was reduced when chemotherapy succeeded to exclusive irradiation. Breast conservation was identical for both groups at the end of primary treatment (82 and 77% for groups I and II, respectively). Of the 191 evaluable patients in the neoadjuvant treatment arm, 65% had an objective response (>50% regression) following four cycles of chemotherapy. The objective response rate to primary irradiation (55 Gy) was 85%. Improved survival figures in the neoadjuvant treatment arm could be the result of the early initiation of chemotherapy, but we cannot exclude that this difference might be attributable to a slightly more aggressive treatment. So far, the trend in favour of decreased metastases was not statistically significant. The local control appeared similar in both subgroups.

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Breast cancer is one of the most common challenges for women's health. Until now, neoadjuvant chemotherapy is a standard approach in locally advanced breast cancer (LABC), as it increases the probability of breast-conserving surgery (BCS). This study aimed to compare the survival rate in neoadjuvant and adjuvant groups to suggest a better treatment strategy for locally advanced breast cancer.
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The 5 and 10 years survival rates of neoadjuvant and adjuvant groups were 87 ± 0.04, 80 ± 0.07% and 87 ± 0.02, 83 ± 0.03%, respectively. Statistical analysis results with the mentioned treatment strategies did not show any significant difference in overall survival.
The result of this study on LABC patients demonstrated that compared to surgery first following adjuvant chemotherapy, the neoadjuvant chemotherapy has several benefits, including downstaging and more BCS, with no statistically significant difference in the overall survival rate of the patients.
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PURPOSE: The purpose of this study was to develop computational algorithms to best determine tumor responses early after the start of neoadjuvant chemotherapy, based on quantitative ultrasound (QUS) and textural analysis in patients with locally advanced breast cancer (LABC). METHODS: A total of 100 LABC patients treated with neoadjuvant chemotherapy were included in this study. Breast tumors were scanned with a clinical ultrasound system prior to treatment, during the first, fourth and eighth weeks of treatment, and prior to surgery. QUS parameters were calculated from ultrasound radio frequency data within tumor regions. Texture features were extracted from each QUS parametric map. Patients were classified into two groups based on identified clinical/pathological response: responders and non-responders. In order to differentiate treatment responders, three multi-feature response classification algorithms, namely a linear discriminant, a k-nearest-neighbor and a nonlinear support vector machine classifier were compared. RESULTS: All algorithms distinguished responders and non-responders with accuracies ranging between 68% and 92%. In particular, support vector machine performed the best in differentiating responders from non-responders with accuracies of 78%, 90% and 92% at weeks 1, 4 and 8 after the start of treatment, respectively. The most relevant features in separating the two response groups at early stages (weeks 1and 4) were texture features and at a later stage (week 8) were mean QUS parameters, particularly ultrasound backscatter intensity-based parameters. CONCLUSION: An early stage treatment response prediction model developed by quantitative ultrasound and texture analysis combined with modern computational methods permits offering effective alternatives to standard treatment for refractory patients.
A Review of the Impact of Neoadjuvant Chemotherapy on Breast Surgery Practice and Outcomes
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Citation Excerpt :
The timing of delivery of NAC also facilitates other aspects of care, such as genetic testing, fertility preservation, and immediate breast reconstruction.14 Several studies have demonstrated an increased use of BCS compared with mastectomy in patients treated with NAC; the NSABP-B18 trial demonstrated an increased rate of BCS from 60% to 68% post-neoadjuvant therapy; trials from the Royal Marsden reported an increase from 78% to 89% and trials from the Curie Institute reported an increased BCS rate of 82% from 77%.15-17 The use of BCS in patients receiving chemotherapy increased from 49.6% in 2005 to 69.2% in 2014 in our institution.
Neoadjuvant chemotherapy (NAC) is increasingly used in locally advanced breast cancer as it facilitates breast conserving surgery (BCS) and allows surgical treatment of patients considered inoperable at baseline. The aim of this study was to assess the trends in breast cancer management with regard to the administration of NAC and adjuvant chemotherapy and the effect this has on surgical practice, patient outcomes, and patterns of disease recurrence.
Patients treated with chemotherapy from 2005 to 2014 were identified from a prospectively maintained database. Clinicopathologic details, timing of chemotherapy delivery, and surgical procedures carried out were analyzed.
A total of 1619 patients were included in the study. The NAC group (n = 383) had a higher T stage (P < .001) and higher grade disease than the adjuvant group (P = .017). Luminal A breast cancer was less likely to be treated by NAC. The proportion of patients treated with NAC has increased from 12.1% in 2005 to 48.3% in 2014 (P < .001). There was an increase in the BCS rate over time (P = .002); however, a higher proportion of the neoadjuvant group (55.5%) underwent mastectomy. Timing of chemotherapy influenced the type of reconstructive procedure carried out (P = .003).
The number of patients with breast cancer being treated with NAC is increasing, which is influencing the increasing rate of BCS, though mastectomy is still central to the surgical management of those in receipt of NAC.
Predictive factors associated with involved margins in breast cancer treated with neoadjuvant chemotherapy followed by breast-conserving therapy
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: This study sought to identify predictive factors of involved surgical margins in breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NAC) to help guide the surgical procedure.
: Retrospective study of patients who had BCS after NAC between January 2008 and December 2013. Outcome measure: tumor-involved margin, defined by tumor cells on ink for invasive cancer and tumor-free margin < 2 mm for DCIS.
: Ninety-seven patients were included. The median age of patients was 46 years old [28–71]. The initial average tumor size was 47.8 mm [+/- 18.6]. Twelve patients (12.4%) had involved tumor margins on final histology after BCS and NAC. According to the multivariate model including only preoperative variables of positive margins, initial ultrasound tumor size ≤ 27 mm (p = 0.045) and low SBR grade (p = 0.009) were independently associated with tumor-involved margins. According to the multivariate model including pre- and postoperative variables of positive margins, ductal carcinomain situ was also independently associated with tumor-involved margins (p = 0.021).
: Initial ultrasound tumor size ≤ 27 mm and low SBR grade were independently associated with tumor-involved margins. These preoperative data were very helpful to guide the surgical procedure in breast cancer.
Adjuvant and neoadjuvant cancer therapies: A historical review and a rational approach to understand outcomes
2019, Seminars in Oncology
Citation Excerpt :
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Impact of neoadjuvant chemotherapy and pathological complete response on eligibility for breast-conserving surgery in patients with early breast cancer: A meta-analysis
2018, European Journal of Cancer
We conducted a meta-analysis of randomised trials evaluating pathological complete response (pCR) and surgical outcomes after neoadjuvant systemic therapy (NST) in patients with early breast cancer (EBC).
The primary outcome was breast-conserving surgery (BCT) rate. Secondary outcomes were pCR rate and association to BCT. Meta-analyses were performed using random effects models that use inverse-variance weighting for each treatment arm based on evaluable patients. Point estimates are reported with 95% confidence interval (CI), and p < 0.05 was considered statistically significant.
Thirty-six studies were identified (N = 12,311 patients). We selected for the analysis 16 of 36 studies reporting both pCR and BCT for at least one treatment arm. Arms per study ranged from one to six; 42 independent units were available to evaluate the association between pCR and BCT. BCT rate ranged 5–76% across arms with an average BCT of 57% (95% CI 52–62%). Significant heterogeneity was observed among the trials (Cochrane Q = 787, p < 0.001, I² = 97%). In the meta-regression model, BCT rates were not significantly associated with year of first patient-in (p = 0.89), grade (p = 0.93) and hormone-receptor status (p = 0.39). Clinical N-stage (p = 0.01) and human epidermal growth factor receptor (HER2) status (p = 0.03) were significantly associated with BCT. pCR rate ranged 3–60% across studies. The average pCR across all study arms was 24% (95% CI 19–29%). No association was observed between pCR rate in a study arm and the resulting BCT rate in a univariate model (p = 0.34) nor after adjusting for HER2 and clinical nodal status (p = 0.82). In the subset of 14 multi-arm studies, no significant association was seen between the differences in pCR and BCT between treatment arms (p = 0.27).
pCR does not increase BCT in patients receiving NST for EBC.

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PaperNeoadjuvant versus adjuvant chemotherapy in premenopausal patients with tumours considered too large for breast conserving surgery: Preliminary results of a randomised trial: S6

Abstract

Ann Oncol

Eur J Cancer

Eur J Cancer

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiatt Oncol Biol Phys

Eur J Cancer Clin Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Eur J Cancer

Concepts for treatment of micrometastases in murine systems

Am J Roentgenol

Surgical adjuvant chemotherapy of metastatic murine tumors

Cancer

A role for chemotherapy as an adjunct to surgery

Cancer Res

Influence of the interval between primary tumor removal and chemotherapy on kinetics and growth of metastases

Cancer Res

The cell cycle and chemotherapy of cancer

The potential for murine tumor models in surgical adjuvant chemotherapy

Cancer Chemother Rep

Success and failure in the treatment of solid tumors

Cancer Chemother Rep

Surgery, cancer chemotherapy, host defenses and tumor size

J Natl Cancer Inst

Experimental therapeutics and kinetics: selection and overgrowth of specifically and permanently drug-resistant tumor cells

Paper
Neoadjuvant versus adjuvant chemotherapy in premenopausal patients with tumours considered too large for breast conserving surgery: Preliminary results of a randomised trial: S6