ESMO Guidelines Recommend Personalized Treatment and Multidisciplinary Decision Making in Breast Cancer

Giuseppe Curigliano, MD, PhD

Irrespective of subtype, the management of metastatic breast cancer requires nuanced and multidisciplinary decision making to optimize and personalize locoregional, systemic, and supportive care, according to the ESMO Clinical Practice Guidelines for the diagnosis, staging, and treatment of patients with metastatic breast cancer that was published in the Annals of Oncology.¹

“The rapid pace at which scientific knowledge is currently advancing means that new evidence may emerge between the time at which documents like the ESMO Clinical Practice Guidelines are developed and their eventual publication and use by clinicians,” Giuseppe Curigliano, MD, PhD, an associate professor of medical oncology at the University of Milano, head of the Division of Early Drug Development at the European Institute of Oncology, IRCCS, in Italy, and chair of the ESMO Guidelines Committee, said in a news release.²

“The up-to-date guideline on metastatic breast cancer was therefore designed to integrate even the most recent, potentially practice-changing data by providing graded recommendations for different treatment choices according to the levels of evidence available to support them, based on their rating within the ESMO Magnitude of Clinical Benefit Scale and the ESMO Scale for the Clinical Actionability of Molecular Targets,” Curigliano added.

Diagnosis and Staging Recommendations

Although survival outcomes have improved for patients with metastatic breast cancer, 5-year survival rates remain around 38%.¹ Therefore, optimization of available therapies is needed to maintain and further improve outcomes for patients. As such, establishing international guidelines could help to standardize treatment options and outcomes across the world.

The guidelines include a proposed diagnostic work-up and staging flow chart. It states that all patients with newly diagnosed or current metastatic breast cancer should have a biopsy of their metastatic lesion to confirm histology and reassess biomarker status, such as estrogen receptor (ER), progesterone receptor (PR), and HER2 status. Additionally, tumor heterogeneity should be considered for each new line of treatment.

Other therapeutically relevant biomarkers should be routinely tested for, including germline BRCA1/2 mutations in HER2-negative metastatic breast cancer, PD-L1 status in triple-negative breast cancer (TNBC), and PIK3CA mutations in ER/PR-positive, HER2-negative metastatic disease. Genomic profiling by tumor tissue or circulating tumor DNA should be performed when results could change treatment selection.

Imaging for staging and risk assessment should incorporate at least a CT scan of the chest and abdomen and a bone scintigraphy. Treatment should be initiated no more than 4 weeks after imaging and response evaluation should occur every 2 to 4 months.

Additionally, brain imaging should not be routinely performed for all asymptomatic patients at diagnosis or during disease monitoring; however, subtype-oriented brain imaging can be considered if the presence of central nervous system metastases will alter treatment decisions for patients with HER2-positive breast cancer or TNBC that have a higher rate of brain metastases. Symptomatic patients should always undergo brain imaging.

Disease Management Recommendations

ER+/HER2- Metastatic Breast Cancer

Patients with ER-positive, HER2-negative metastatic breast cancer should receive estrogen therapy with an aromatase inhibitor or fulvestrant (Faslodex) plus a CDK4/6 inhibitor in the frontline setting. In patients for whom organ failure is imminent, chemotherapy followed by maintenance or next-line endocrine therapy plus a CDK4/6 inhibitor should be considered.

Upon progression, patients without a risk of organ failure are eligible for fulvestrant plus a CDK4/6 inhibitor if not previously used, everolimus/exemestane or everolimus/fulvestrant, fulvestrant/alpelisib (Piqray) if PIK3CA mutated, or a PARP inhibitor if BRCA/PALB2 mutated. Chemotherapy should be given upon progression after several lines of endocrine therapy with or without targeted therapies.

HER2+ Metastatic Breast Cancer

In the first-line setting, patients with hormone receptor (HR)–positive, HER2-positive disease with chemotherapy contraindications should receive trastuzumab (Herceptin) with or without pertuzumab (Perjeta) and endocrine therapy. Patients with HR-negative, HER2-positive disease with chemotherapy contraindications should receive trastuzumab/pertuzumab. Regardless of HR status, patients without chemotherapy contraindications should receive docetaxel or paclitaxel, trastuzumab, and pertuzumab followed by trastuzumab, pertuzumab, and endocrine therapy.

Second-line treatment for patients with active brain metastases for whom local intervention is indicated are eligible for resection with or without stereotactic radiotherapy or whole-beam radiation therapy based on the number of active brain metastases. In patients for whom local intervention is not indicated or for those without active brain metastases, tucatinib (Tukysa)/capecitabine/trastuzumab or fam-trastuzumab deruxtecan-nxki (Enhertu) is indicated. Third-line and beyond treatment recommendations are the same for patients with active brain metastases; however, in patients without active brain metastases, ado-trastuzumab emtansine (T-DM1; Kadcyla) can be considered in the third-line setting, followed by lapatinib (Tykerb)/trastuzumab, trastuzumab/chemotherapy, margetuximab (Margenza)/chemotherapy, or neratinib (Nerlynx)/chemotherapy in subsequent lines of therapy.

TNBC

Patients with PD-L1–positive TNBC should receive atezolizumab (Tecentriq) plus nab-paclitaxel (Abraxane) or pembrolizumab (Keytruda) plus chemotherapy. Patients with BRCA-mutated TNBC should receive chemotherapy- or PARP inhibitor–based treatment. Patients with PD-L1–negative, BRCA wild-type TNBC should receive anthracycline/taxane–based therapy, taxane/bevacizumab (Avastin), or capecitabine/bevacizumab if organ failure is imminent, or taxane or anthracycline monotherapy if organ failure is not imminent.

Upon progression, sacituzumab govitecan-hziy (Trodelvy) or chemotherapy is indicated for all patients followed by chemotherapy with eribulin (Halaven), capecitabine, or vinorelbine.

Hereditary Breast Cancer and Oligometastatic Disease

Patients with HER2-negative metastatic breast cancer who harbor germline pathogenic or likely pathogenic variants in BRCA1/2 should be considered for PARP inhibitor therapy with olaparib (Lynparza) or talazoparib (Talzenna) irrespective of HR status.

In patients for whom oligometastatic disease is confirmed, a multidisciplinary team should consider the site of metastases, management of primary tumor and axilla, systemic treatment options, and localized approaches when making treatment decisions for patients.

Supportive and Palliative Care Recommendations

In all cases of metastatic breast cancer, multidisciplinary care should be utilized. Moreover, specialized oncology or breast care nurses should proactively screen patients for treatment-emergent toxicities, which should be managed accordingly. Quality-of-life assessments should be incorporated into the evaluation of treatment efficacy, and dose reductions or delays should be utilized in cases of toxicity.

It is important to incorporate palliative care early in inpatient and outpatient settings. With the rising median overall survival in metastatic breast cancer, patients are more likely to develop metastases in several areas of the body. As such, optimal symptom control, as well as psychological, social, and spiritual support should be implemented after patients receive best available therapy.

Shared-decision making between the provider and patient/family should be utilized to educate, establish goals and expectations, and optimize care.

Finally, health care professionals should have mental health support available to them to ensure they are able to provide sensitive and effective care to patients.

References

1. Gennari A, André F, Barrios CH, et al. ESMO clinical practice guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann Oncol. Published October 13, 2021. Accessed November 2, 2021. doi:10.1016/j.annonc.2021.09.019
2. Metastatic breast cancer: new ESMO guideline with evidence-based recommendations [ESMO press release]. News release. ESMO. October 19, 2021. Accessed November 2, 2021. https://bit.ly/3mBjDjo