Impact of the Delayed Initiation of Adjuvant Chemotherapy in the Outcome of Triple Negative Breast Cancer

doi:10.1016/j.clbc.2020.09.008

Clinical Breast Cancer

Volume 21, Issue 3, June 2021, Pages 239-246.e4

https://doi.org/10.1016/j.clbc.2020.09.008 Get rights and content

Abstract

Background

Adjuvant chemotherapy decreases the recurrence risk and improves survival rates; however, it is unclear whether a delayed initiation is associated with adverse outcomes, especially in triple negative breast cancer (TNBC). In this study, we evaluated the influence of the time to start adjuvant chemotherapy (TTC) in the outcomes of TNBC.

Patients and Methods

We retrospectively analyzed 15 years of data from patients with TNBC who received adjuvant chemotherapy at the Instituto Nacional de Enfermedades Neoplasicas (Lima, Peru). TTC was categorized into 4 groups: ≤ 30, 31 to 60, 61 to 90, and ≥ 91 days. We evaluated overall survival (OS) and distant recurrence-free survival (DRFS). Cox proportional hazard models were used to identify prognostic factors.

Results

In total, 687 patients were included. The mean age at diagnosis was 49.1 years (SD, 11.8 years), and most (62.6%) patients had pathologic stage T2. The median TTC was 48.1 days (SD, 27.4 days); 189 (27.5%) received chemotherapy ≤ 30 days; 329 (47.9%), between 31 and 60 days; 115 (16.7%), between 61 and 90 days; and 54 (7.9%) in ≥ 90 days. In the multivariate analysis, a TTC between 31 and 60 days (hazard ratio [HR], 1.78; 95% confidence interval [CI], 1.17-2.72), 61 and 90 days (HR, 2.38; 95%CI, 1.43-3.97), and ≥ 91 days (HR, 2.45; 95% CI, 1.32-4.55) was associated with an increased mortality in contrast with a TTC < 30 days. Although a TTC between 31 and 60 days, 61 and 90 days, and ≥ 91 days was associated with an increased risk of DRFS (HR, 1.86; 95% CI, 1.24-2.79; HR, 2.34, 95% CI, 1.42-3.867; and HR, 3.16; 95% CI, 1.78-5.61, respectively).

Conclusion

A delaying in TTC ≥ 30 days was associated with poorer outcomes. Our data suggest that several efforts should be conducted to avoid a delayed TTC in patients with TNBC.

Introduction

Triple negative breast cancer (TNBC) accounts for 7% to 20% of all breast cancer cases,¹^,² with a higher prevalence among Hispanic, African-American, and younger women.³ As an aggressive phenotype, TNBC exhibits a high probability of early tumor relapse after diagnosis, increased risk to develop distant metastases, and death.²^,4, 5, 6 Despite the progress in the management of BC leading to improved outcomes, the prognosis for patients with TNBC remains poor compared with patients with luminal or human epidermal growth factor receptor 2-positive (HER2⁺) tumors.

Surgery preceded or followed by anthracycline and taxane-based chemotherapy is still the standard of care in TNBC⁷; however, the optimal time for the initiation of adjuvant chemotherapy (TTC) is not clearly defined. Some retrospective studies have suggested that a delayed TTC is associated with worse outcomes,8, 9, 10 particularly in terms of overall survival (OS).⁹

To date, all the studies addressing this issue are done retrospectively because answering this question in a prospective manner is unethical and unfeasible. Also, they did not include Latin-American patients, who have different epidemiology characteristics, such as a younger age of presentation and more frequent TNBC tumors.¹¹^,¹² We conducted a retrospective analysis based on our single-institution data to provide additional evidence about the effect of delayed initiation of chemotherapy after surgery in the outcomes of TNBC and the factors associated with TTC.

Section snippets

Design and Study Population

A total of 17,063 patients with BC were treated from January 2000 to December 2014 at the Instituto Nacional de Enfermedades Neoplasicas (INEN) in Lima, Peru.¹³ We identified 2007 patients diagnosed with TNBC, whose pathologic diagnosis was confirmed in the institution, considering TNBC as the absence of estrogen receptor (ER) and progesterone receptor (PR) evaluated by immunohistochemistry (IHC), and the absence of overexpression of the HER2 protein by IHC or its genetic amplification

General Patient Characteristics

Of 2007 patients with TNBC, 687 were analyzed in this study after applying the eligibility criteria. The mean age of the participants was 49.1 years (SD, 11.8 years), 20.1% (n = 138) had comorbidities, and 41.8% (n = 287) were diagnosed during 2005 to 2009. Most (62.9%; n = 432) of the patients underwent mastectomy, and 37.1% (n = 255) underwent conservative surgery; of these, 18% (n = 124) had resection margins. Most (62.6%) patients were pT2, and 54.6% (n = 375) were given anthracycline and

Discussion

It is well-known that TNBC has worse outcomes in comparison with other BC subtypes. These tumors are characterized by an aggressive behavior and a higher proliferation index.¹⁴ Because there is no targeted therapy available for this breast cancer subtype, chemotherapy has been proven as an effective treatment.¹⁵^,¹⁶ This study shows that a delay in chemotherapy initiation of more than 30 days has a negative impact on the outcomes of patients with TNBC in terms of OS and DRFS.

Regarding OS,

Conclusion

Despite the limitations of our study, the results and the previously published evidence showed the greater the delay, the worse the outcomes. A timely treatment can change the prognosis of patients with TNBC, from a 10-year OS of 82% for TTC ≤ 30 days to 65.1% for TTC ≥ 91 days. Clearly, it is important to implement strategies to avoid delays in treatment, especially in aggressive types of cancers such as TNBC.

Disclosure

The authors have stated that they have no conflicts of interest.

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View all citing articles on Scopus

View full text

Original StudyImpact of the Delayed Initiation of Adjuvant Chemotherapy in the Outcome of Triple Negative Breast Cancer

Abstract

Background

Patients and Methods

Results

Conclusion

Introduction

Section snippets

Design and Study Population

General Patient Characteristics

Discussion

Conclusion

Disclosure

Clin Breast Cancer

Eur J Cancer

Ann Oncol

Eur J Surg Oncol

Triple negative breast tumors in African-American and Hispanic/Latina Women are high in CD44+, low in CD24+, and have loss of PTEN

PLoS One

Presence of a growth-stimulating factor in serum following primary tumor removal in mice

Cancer Res

Introduction

Cancer Metast Rev

A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate

Cancer Treat Rep

Clinical impact of delaying initiation of adjuvant chemotherapy in patients with breast cancer

J Clin Oncol

Delayed initiation of adjuvant chemotherapy among patients with breast cancer

JAMA Oncol

Influence of delayed initiation of adjuvant chemotherapy on breast cancer survival is subtype-dependent

Oncotarget

Effect of Ki-67 assessment in the distribution of breast cancer subtypes: evaluation in a cohort of Latin American patients

Mol Clin Oncol

Original Study
Impact of the Delayed Initiation of Adjuvant Chemotherapy in the Outcome of Triple Negative Breast Cancer