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Delayed initiation of adjuvant chemotherapy associated with worse outcomes in patients with triple-negative breast cancer

Oncology
15 days ago, OP Editor

Triple-negative breast cancer (TNBC) accounts for approximately 10-15% of diagnosed breast cancers, one of the most common solid tumors affecting women.1 The European Society for Medical Oncology (ESMO) guidelines suggest that triple negative tumors benefit from adjuvant chemotherapy, with the possible exclusion of low-risk ‘special histological subtypes’,2 and a retrospective study analyzed that a delayed initiation of adjuvant chemotherapy was associated with worse outcomes in TNBC.3 The results were presented at the 41st San Antonio Breast Cancer Symposium (SABCS).

TNBC is defined by the lack of expression of three receptors: estrogen, progesterone, and human epidermal growth factor 2 (HER2).4 It is a typically aggressive disease and with little clinical success in its treatment, development of optimal therapeutic strategies are crucial for lessening disease burden.4 Neoadjuvant and adjuvant chemotherapy regimens are considered as typical systemic treatment for TNBC, with the standard of care being anthracycline- and taxane-based.4 Studies have shown that adjuvant chemotherapy decreased the risk of recurrence and improved overall survival in breast cancer patients, and adjuvant chemotherapy is recommended for primary tumors larger than 0.5cm in TNBC due to its aggressive behavior.3,4

A retrospective study, which was presented at the 41st SABCS, found that a delay in the initiation of adjuvant chemotherapy following surgery had an impact on survival.3 Lead investigator Dr. Zaida Morante, medical oncologist at Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru, explained that there is often a delay in starting adjuvant chemotherapy in patients with TNBC, despite most guidelines recommending starting therapy 4-6 weeks after surgery for any type of cancer.5

Some guidelines recommend starting as soon as clinically possible after surgery, but the optimal time is still unknown, and there was no information regarding whether a delay in the initiation could affect overall outcomes.3,5 Medical records from 687 patients with stages 1-3 TNBC who received adjuvant chemotherapy after surgery were analyzed, and it was observed that the 10-year disease-free survival (DFS) rate decreased with an increase in time to adjuvant chemotherapy (TTC).5

The median time to therapy was 41 days, with 27.5% patients receiving chemotherapy on or within 30 days, and 7.9% patients receiving adjuvant therapy beyond 90 days.6 The data showed that amongst those who received chemotherapy on or before 30 days, the 10-year DFS was 81.4%, but DFS rate was much lower in those patients who received therapy after 90 days, with only 68.1% patients (p=0.005).6

Ten-year overall survival (OS) was also affected with a longer TTC, especially when comparing patients who received therapy on or before 30 days and those who received therapy beyond 90 days (82% vs. 65.1% respectively, HR=2.79; 95% CI: 1.418-5.506; p=0.003).6 The multivariate analysis also showed that TTC was an independent prognostic factor for recurrence-free survival (RFS) and OS, and a risk of disease recurrence was observed to increase by 92% in those who delayed treatment for 31-60 days after surgery, and by 147% in those who delayed treatment for more than 90 days, compared to those who received therapy within the first 30 days after surgery.5

A main limitation of this retrospective study acknowledged by the investigators was that this analysis was only of a single institution.3 However, the conclusion drawn from the analysis was that a delayed initiation of chemotherapy in TNBC patients of over 30 days is associated with a decrease in RFS and OS, with the greater the delay, the worse the outcome.6 “Our data show that it must be a priority for patients with TNBC to begin adjuvant chemotherapy within 30 days of completing surgery. After this period of time, the benefit of chemotherapy is significantly diminished,” explained Dr. Morante.3

1. Lebert J, Lester R, Powell E et al. Advances in the systemic treatment of triple-negative breast cancer. Curr Oncol. 2018;25(Suppl 1):S142-S150.

2. Senkus E, Kyriakides S, Ohno S et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26 Suppl 5:v8-30.

3. Cavallo J. SABCS 2018: Delayed Initiation of Adjuvant Chemotherapy Associated With Worse Outcomes in Patients with Triple-Negative Breast Cancer. ASCO Post. (Accessed December 27 2018, at http://www.ascopost.com/News/59545).

4. Park J, Ahn J, Kim S. How shall we treat early triple-negative breast cancer (TNBC): from the current standard to upcoming immuno-molecular strategies. ESMO Open. 2018;3(Suppl1):e000357.

5. San Antonio Breast Cancer Symposium – Press Release. Delaying Adjuvant Chemotherapy Associated With Worse Outcomes for Patients with Triple-negative Breast Cancer. (Accessed December 27 2018, at https://www.sabcs.org/sabcs/2018/pressreleases/2_qw35g3twh9m8_Delaying%20Adjuvant%20
Chemotherapy%20Associated%20With%20Worse%20Outcomes%20for%20Patients%20With%20Triple-negative%20Breast%20Cancer.pdf
).

6. Morante Z, Ruiz Rm, De la Cruz K et al. Abstract: Delaying Adjuvant Chemotherapy Associated With Worse Outcomes for Patients with Triple-negative Breast Cancer. (Accessed December 27 2018, at https://www.abstracts2view.com/sabcs18/view.php?nu=SABCS18L_1578&terms=).

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