Breast cancer is the most common type of cancer in women worldwide and triple negative breast cancer (TNBC) subtype is the most aggressive. The most used chemotherapy drug is paclitaxel (PX), which, when used at high doses, generates numerous adverse effects. To avoid it, metronomic chemotherapy (MC) arises as an alternative treatment schedule involving much lower drug doses administered at shorter intervals, reducing adverse effects and increasing antitumor effectiveness. Another approach to improve the efficiency of antitumor treatment is the use of selective targets present only in tumor cells. We demonstrate that muscarinic receptors are expressed in breast tumor cells but absent in non-tumor breast cells, making them a potential therapeutic target. Here we evaluated the effectiveness of a MC combining low doses of PX (10-8M) and the muscarinic agonist carbachol (10-11M) in human TNBC MDA-MB231 cells. By MTT assays we demonstrated that MC was as effective as conventional chemotherapy (CC) with PX (10-6M) in reducing cell viability in vitro (control: 100.0±10.2%; MC: 25.0±8.1%; CC: 11.9±12.1%). Furthermore, the residual cells after treatment with MC were more sensitive to a new cycle with PX evaluated by IC50 (control: 7.6×10-5 M; MC: 9.3×10-9 M; CC: 5.8×10-6 M). Since this effect may occur by the modulation of the drug transporter ABCG2 expression, we determined by Western blot (Wb) assays that MC reduced its expression (control: 100±9%; MC: 18±6%). Since angiogenesis is necessary for tumor growth, by Wb we evaluated VEGF-A levels and determined that MC significantly reduced it (control: 100±25%; MC: 50±23%) and reduced angiogenesis in vivo (No. vessels/cm2 skin) (normal skin: 3.0±0.1; cells alone: 4.0±0.1; MC: 2.9±0.2; CC: 4.3±0.2). Our results demonstrate that changing a conventional chemotherapy administration scheme by a metronomic one is a plausible alternative for TNBC treatment.