What treatment would you provide for a patient with bilateral synchronous locally advanced cT4dN0 TNBC and cT1b ER+ HER2+ breast cancer?

Yes, the TNBC seems to be locally advanced and being T4d, would qualify for the KEYNOTE-522 regimen. The HER-2 positive cancer is small and clinically lymph node negative, so upfront surgery followed by adjuvant anti HER-2 therapy based on APT trial would be reasonable. But since the patient would have received neoadjuvant paclitaxel as part of KEYNOTE-522 regimen, I may offer adjuvant Trastuzumab without chemotherapy. I would also offer adjuvant pembrolizumab regardless of pCR since all groups benefited from adjuvant pembrolizumab based on KEYNOTE 522 results. 

The incidence of synchronous bilateral breast cancer is 1.0% to 2.6%, while the risk of developing metachronous contralateral carcinoma can be 0.9% per year, with a cumulative risk of 12% at 15 years. Lobular histology, family history, young age at diagnosis, and BRCA mutations have been associated with an increased incidence of bilateral presentation. (Copur et al., PMID 28412779) Despite the lack of adjuvant data, safety and efficacy of the pembrolizumab and trastuzumab combination has been tested in advanced/metastatic gastric/gastroesophageal cancer (KEYNOTE-811), as well as in advanced/metastatic breast cancer. (PANACEA) Thus, in this particular case, it is logical to use this combination in the adjuvant setting.

For the sake of completeness and multidisciplinary management of this case, a few more questions need to be addressed. The T4d (inflammatory) nature of the TNBC breast cancer will require a mastectomy even if the cancer responded well to neoadjuvant chemotherapy to be followed by radiation therapy to the chest wall and lymph nodes, with no immediate reconstruction recommendations. T1c TPBC can be treated with lumpectomy/sentinel node followed by postmastectomy radiation and added adjuvant hormonal therapy. Given bilateral presentation, a genetic counseling and genetic testing would be indicated and might guide both surgical as well as the adjuvant treatment options (if BRCA positive with consideration of adjuvant PARP inhibitor).