Session 12

Local and systemic therapies

CHAIRS

Elisa Bal de Kier Joffe

Institute of
Oncology A H Roffo

Roxana Schillaci

Instituto de Biología y
Medicina Experimental

Pablo Mando

CEMIC

SPEAKERS

Oligometastasis—The Impact of Local Therapy On Systemic Disease

Catherine Park

The development of systemic disease, or metastasis, has been long viewed as heralding the end of survival from cancer. However, clinically, it has been observed for decades that some patients may harbor metastatic disease for long periods of time while other patients develop metastasis and succumb to disease rapidly, reflecting a spectrum of metastatic disease spread and virulence. Much of our ability to detect metastasis relies on advanced imaging techniques, which also have their limitations. Traditionally, treatment of metastasis with local therapies, (eg, surgery and radiation) were focused on palliation of pain or symptoms. In recent years, several trials have addressed the question of whether local ablative treatment of metastasis could improve outcomes in patients with limited metastatic disease, or oligometastasis. The treatment of oligometastasis with either surgery or ablative radiation resulted in improved long term disease control and survival in patients with several tumor types. This field is still evolving, and areas still being actively investigated include definitions of oligometastasis, advanced imaging techniques to identify subclinical metastasis and the underlying biology.

Treatment Of HER2 Positive Tumors

Maria Victoria Costanzo

The HER2 positive breast cancer is a very heterogeneus clinically and biologically disease. Almost all breast cancer subtypes are included in this type determined by inmunohistoquimically. The treatment of early disease with neoadjuvant treatment is practice changing. We now know the importance of archiving pCR and the changing characteristics of the residual disease. The use double blockade with pertuzumab, trastuzumab and chemotherapy has augmented the proportion of patients with pCR. Another strategy is to extended adjuvant treatment with neratinib in pacients with residual disease ER+ or high risk ER + disease. The use of Trastuzumab Emtansine in patients with residual disease and bad prognosis is also practice changing. Patienst with a disease with less risk may descalate treatment, no double blockade and less chemotherapy or even shorter antibody duration. In the setting of advanced disease, many new treatments have emerged last 2 years: Trastuzumab deruxtecan, Tucatinib, Neratinib and Margentuximab. They have different characteristics but all they show responses in progressive disease after pertuzumab and trastuzumab and trastuzumab emtamsine. The change is how we sequence them and the introduccion in early disease to cure more patients.

Immunotherapy for triple negative breast cancer

Florencia Perazzo

Triple-negative breast cancer (TNBC) is an aggressive subtype of mammary carcinoma, which occurs in approximately 15% of diagnosed breast cancers. Thus, more effective therapeutic options are sorely needed. In recent years, advances in immunotherapy have yielded potential new therapeutic strategies which may be a viable option for the subset of immune activated TNBC. In early TNBC, pembrolizumab and atezolizumab have been tested in combination with neoadjuvant chemotherapy, resulting in higher complete pathologic response rates, regardless of PD-L1 status. Phase III clinical trials have shown a progression-free survival benefit with this two drugs in combination with chemotherapy in first line metastatic PD-L1 positive TNBC patients. These findings establish proof of principle for immunotherapy in both early and advanced TNBC. However, as efficacy is still low, we are in need of developing more active immunotherapy combination regimens and more refined biomarkers that optimally identify patients most likely to benefit from immunotherapy.

MCL-1 is a clinically targetable vulnerability in breast cancer

(Selected from posters)

Matthew L. Winder

Pro-survival BCL-2 family protein MCL-1 is one of the most frequently amplified genes in breast cancer, particularly in ‘basal-like’ triple-negative breast cancer (TNBC). The outcome of most patients diagnosed with TNBC is especially poor, as post-surgical disease recurrence and mortality occurs in 50-80% of cases. The dismal prognosis of TNBC patients is caused by (1) increased propensity for metastasis; (2) high rates of post-treatment relapse and/or therapeutic resistance; (3) a paucity of targeted treatment options.

We have previously demonstrated that MCL-1 protein expression in a large breast cancer tissue microarray cohort was predictive of poor outcome in treatment naive TNBC, thus representing an attractive therapeutic opportunity.

We demonstrate that targeting MCL-1 restricts mammary tumour formation and promotes regression of established tumours in vivo. This is due to the canonical function of MCL-1 in the intrinsic apoptotic pathway where we uncover a requirement for MCL-1 in breast cancer stemness, and in silico analysis of breast cancer datasets highlights the correlative relationship between MCL-1 expression and markers of cancer stem-like cell behaviour. Targeted inhibitors of MCL-1 are currently undergoing clinical trials for the treatment of haematological malignancies, and our evidence suggests that targeting MCL-1 may offer a valuable new therapeutic option in TNBC patients.