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CD4+ regulatory T cells (Treg) have a detrimental effect in cancer-immunity, as they suppress tumor-specific effector T cells (Teff) hindering tumor eradication. Indeed, increased Treg numbers in various cancer types, including breast cancer, correlate with poor patient prognosis. Based on animal studies, Treg enrichment may result from the expansion of thymic natural Treg but also through the conversion of conventional T cells (Tconv) into induced Treg (iTreg) under tumor-suppressive conditions. However, little is known about tumor-specific iTreg generation in humans and its impact on the TCR repertoire of peripheral Treg. Therefore, we compared the TCRβ repertoire of total Treg and tumor-reactive Teff or total Tconv from peripheral blood of breast cancer patients or healthy individuals, as negative control, for the identification of overlapping TCRs, representing iTreg. In addition, using high-throughput single-cell transcriptome sequencing combined with TCRαβ characterization we analyze the functional profile of individual Treg and Tconv clones, in order to elucidate their specific role in anti-tumor immunity in humans. No major TCR overlap was observed between Treg and tumor-reactive Teff or total Tconv in peripheral blood of patients and healthy individuals, arguing against the existence of tumor-specific iTreg in the circulation. Nevertheless, within the tumor Treg and Tconv shared dominant highly-expanded clones, representing 10–65% of the tumor-infiltrating Treg population but with no effect in peripheral blood. Taken together, our data suggest that intratumoral secondary Treg conversion from dominant Tconv clones may have a major impact on the tumor-infiltrating but not on the circulating Treg population.