Can common BP-lowering drugs keep breast cancer in check?

Angiotensin receptor blockers (ARBs), used to treat high blood pressure (BP), appear to confer dose-dependent survival benefits on breast cancer patients when taken either prior to or after diagnosis, a study has found.

Aside from ARBs, the postdiagnosis use of several antihypertensive drugs with differing mechanisms of action also produce a decrease in the risk of death. “This suggests that the underlying condition serving as a common indication for usage, ie hypertension and its treatment, may explain the risk association,” the investigators said.

In other words, “good control of hypertension after breast cancer diagnosis might improve prognosis,” they added.

The analysis was based on 73,170 female breast cancer patients from the Finnish Cancer Registry. Of these, 10,900 women died during follow-up, among whom 6,358 (175/1,000) had been users of a BP-lowering drug and 4,542 had been nonusers.

In terms of prediagnostic use, only ARBs showed a survival advantage, lowering the risk of breast cancer death by 24 percent relative to nonuse (hazard ratio [HR], 0.76, 95 percent confidence interval [CI], 0.69–0.82). [Cancer Epidemiol Biomarkers Prev 2020;29:2376-2382]

The survival benefit further improved with increasing amount of ARB use. The corresponding HRs vs nonuse were 0.82 (95 percent CI, 0.73–0.93) with 0–252 defined daily doses (DDDs)/year, 0.72 (95 percent CI, 0.63–0.82) with 252–394 DDDs/year, 0.71 (95 percent CI, 0.61–0.82) with ≥394 DDDs/year.

Meanwhile, when looking at postdiagnostic use, all of the following antihypertensive drugs exerted a positive dose-dependent effect on breast cancer survival: ARBs (HR, 0.77, 95 percent CI, 0.71–0.84), angiotensin-converting enzyme inhibitors (HR, 0.94, 95 percent CI, 0.88–1.00), beta-blockers (HR, 0.93, 95 percent CI, 0.88–0.98), and calcium channel blockers (HR, 0.93, 95 percent CI, 0.87–0.99). This benefit was most pronounced at the highest tertiles of amount, duration, and intensity of usage.

Patients on ARBs appeared to benefit the most, with decreased mortality persisting for exposures occurring up to 3 years earlier, the investigators noted.

They acknowledged that the findings with BP-lowering drugs could be affected by a healthy-user bias. “Medication users may have a healthier lifestyle in general as compared to nonusers, thus creating a bias favouring the users. However, this kind of bias should not be dose-dependent, therefore the dose-dependent risk associations support causality.”

Despite the presence of several limitations, the study indicates that inhibition of angiotensin receptor subtype 1 (AT₁) could be a promising novel way to affect breast cancer progression, they said. “More research into the role of the AT2-receptor in breast cancer is warranted.”