Doxorubicin, hypertension predict lower breast cancer recurrence

Certain comorbidities such as hypertension and diabetes mellitus (DM), along with locally advanced stage at diagnosis and systemic treatment received (ie, doxorubicin), are significantly associated with tumour recurrences among patients with breast cancer, according to a study presented at the recent ASCO Breakthrough 2023.

Specifically, having hypertension and receiving doxorubicin show the strongest effect for reducing the recurrence rate.

“In this study, we determined the risk factors and predictors of breast cancer tumour recurrence in a tertiary government hospital (Breast Care Center - East Avenue Medical Center) in a third-world country like the Philippines,” said authors Omar Paningbatan Maaño and Mary Claire V Soliman, both from St Luke’s Medical Center, Quezon City, Philippines.

Maaño and Soliman reviewed 529 charts at the Breast Care Center between 2011 and 2017. They selected 474 charts that met the eligibility criteria and obtained demographic and clinicopathologic features from these records. Finally, Cox proportional hazard regression was used to calculate hazard ratios (HRs) of the different variables to compare the recurrence rates.

Patients had a mean age of 50 years at diagnosis and a median body mass index of 25 kg/m². Breast cancer subtypes were HR+/HER2- in 246 (52 percent) patients, HR-/HER2+ in 52 (11 percent), HR+/HER2+ in 81 (17 percent), and HR-/HER2- in 95 (20 percent). [ASCO Breakthrough 2023, abstract 7]

Of the patients, 21.7 percent had hypertension and 7 percent DM. Invasive carcinoma (92.6 percent) was the most common histology, and 42.5 percent had a lymphovascular invasion.

The highest tumour recurrence occurred among those with HR-/HER2+ breast cancer (15.38 percent), followed by HR-/HER2- (11.96 percent), HR+/HER2- (8.54 percent), and HR+/HER2+ (7.41 percent). The median time to recurrence was 47 months with HR+/HER2-, 24 months with HR-/HER2+, 39.5 months with HR+/HER2+, and 47 months with HR-/HER2-.

Moreover, bone (39 percent) and local recurrence (32.37 percent) were the most common sites of recurrence. Two patients with HR-/HER2+ had contralateral breast recurrence.

Cytotoxic agents

Of the patients, 6.7 percent received neoadjuvant systemic therapy, while the rest had adjuvant systemic therapy. Most of them went through modified radical mastectomy (92.8 percent). Among cytotoxic agents used, the most common were cyclophosphamide (96.14 percent), doxorubicin (87.13 percent), docetaxel (53.37 percent), and 5-fluorouracil (37.87 percent).

Notably, only 19.54 percent of patients with HER2+ subtype were treated with trastuzumab.

In univariate analysis, tumour recurrence was found to be significantly impacted by the following factors: hypertension (HR, 0.34, 95 percent confidence interval [CI], 0.13‒0.85; p=0.022), DM (HR, 2.55, 95 percent CI, 1.19‒5.48; p=0.016), stage IIIa (HR, 3.78, 95 percent CI, 1.04‒13.73; p=0.044), IIIb (HR, 9.11, 95 percent CI, 2.46‒33.68; p=0.001), IIIc (HR, 12.59, 95 percent CI, 3.50‒45.22; p<0.001), positive lymph nodes (HR, 1.07, 95 percent CI, 1.02‒1.12; p=0.002), and treatment with doxorubicin (HR, 0.44, 95 percent CI, 0.23‒0.86; p=0.015).

Multivariate analysis revealed that hypertension (HR, 0.32, 95 percent CI, 0.11‒0.94; p=0.038) and doxorubicin (HR, 0.30, 95 percent CI, 0.13‒0.70; p=0.005) were strongly associated with a reduced rate of recurrence, while DM (HR, 7.45, 95 percent CI, 2.85‒19.46; p<0.001) and locally advanced stage (IIIb; HR, 10.97, 95 percent CI, 2.51‒48.06; p=0.001) correlated with a higher recurrence risk.