Would you recommend local therapy for a residual breast tumor after chemotherapy following CR of distant disease in a patient with metastatic disease?

Palliation is one clear indication for treating a primary breast tumor in a patient with metastatic disease and may be considered if the tumor is fungating, painful, and/or bleeding. The second potential indication, which is likely the intent of your question, is to improve long term disease control with local therapy. You are more likely to be successful at accomplishing this in patients with a good prognosis in whom the benefit of local therapy is not outweighed by the competing risk of distant progression. To evaluate this, you need to evaluate the number of metastases, bone only vs. visceral disease, the response to systemic therapy and efficacy of future second-line systemic therapies, the biology of the cancer (ER positive vs ER negative, the metastatic course until this point), and the age and comorbidities of your patient.

With regard to data, most of the retrospective studies show a benefit but these studies are greatly limited by the selection bias that women who receive surgery are more likely to be younger, have smaller tumors, more ER+ disease and lower metastatic burden (see meta-analysis from Petrelli & Barni). There is randomized data from India (Badwe, Lancet Oncol 2015) in which de novo metastatic patients were first treated with systemic therapy and then randomized to surgery vs. no local therapy. With 350 patients randomized, and a median follow up of 23 months, the authors failed to show any difference in OS at 2 years. There is an additional radnomized trial from Turkey (Soren et al Ann Sug Oncol 2018) with 274 patients. They showed no improvement in the primary endpoint of OS at 3 years but with longer study follow up (median 40 months) showed an improvement in median survival and advantages in unplanned subgroups such as young patients and patients with solitary bone only disease. We are awaiting the results of ECOG 2108 (opened February 2011) which randomizes women with intact primary tumors and metastatic disease at any site to early local therapy (surgery plus XRT) vs. no local therapy after initial systemic therapy (acknowledgment to Dr. Seema Khan whose talk at SABCS guided me to much of this data).

The question of whether or not to give adjuvant radiation after a patient has lumpectomy in the setting of well-controlled metastatic disease is yet another important one that comes up not infrequently. One could argue that the benefit of an “adjuvant” therapy aimed at local control is diminished in the setting of known metastatic disease and that one local therapy (surgery without XRT) is sufficient.

In summary, one may consider offering local therapy in patients with asymptomatic primary tumors if distant disease is well-controlled, with the understanding that we are likely not offering a survival benefit. Whether this local therapy should be surgery or radiation or both is not well-studied. In this context, I would certainly push for breast conservation over mastectomy in a patient with known metastatic disease (and no indication for palliative mastectomy) and you may argue that lumpectomy alone is enough when the competing risk of distant metastasis already exists.