Breast cancer is the most frequently occurring cancer in women and the second most common cancer overall, with over 2 million new cases in 2018. It is thanks to today’s array of powerful anti-cancer therapies, the earlier detection of disease, patient screening and cancer prevention programs that 5-year overall survival rates are now at 90%.

While only 2.6% patients at our hospital, the Vall d’Hebron University Hospital (HUVH), are initially diagnosed with advanced disease, other patients may later suffer from cancer relapse and metastatic cell spread. The regular follow-up and close vigilance of patients are thus paramount. In parallel, the early identification, tracking and more precise tackling of disease recurrence and progression, are driven at VHIO by advances at the preclinical, translational and clinical research levels.

Our Breast Cancer Group, directed by Cristina Saura, has just this year embarked upon its second decade. This program is devoted to leading and participating in some of the most relevant multi-center and international clinical trials to assess the efficacy and safety of novel therapies, and enrolls patients in studies with some of the most promising agents including neratinib, SYD985, DS8201, and SERDs. Over the past year, 225 patients have been matched to a particular clinical study designed to assess a novel treatment approach.

Depending on the molecular make-up and specificities of their tumors, some patients may also be molecularly matched to participate in one of VHIO’s broad spectrum of pioneering clinical trials carried out at our Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa” which is directed by Elena Garralda, Principal Investigator of Early Clinical Drug Development. These studies ultimately aim at accelerating discovery into improved clinical outcomes.

For those patients who are unfortunately refractory to standard therapeutic options, Cristina’s team, in  collaboration with researchers of VHIO’s leading Prescreening Program pioneered by our Cancer Genomics, Molecular Oncology, Early Clinical Drug Development, and Oncology Data Science Groups, headed by Ana Vivancos, Paolo Nuciforo, Elena Garralda, and Rodrigo Dienstmann, respectively, strive to identify an alternative and personalized treatment approach based on the specificities of each individual’s disease. At our Breast Cancer Unit, Medical Oncologist and Clinical Investigator, Mafalda Oliveira, leads the clinical analyses of these data. Based on the results obtained, she identifies the best possible treatment option for each patient and manages referral for possible inclusion in one of our early phase studies.

Commenting for VHIO Communications, Cristina Saura, also Head of our Breast Cancer Unit located in the Breast Cancer Center at HUVH, observed, “Around 74% of all clinical trials at VHIO are tailored to breast cancer patients with metastatic disease. While some patients may continue to receive standard therapies, we also seek to extend survival and ensure that our patients can live with their respective cancer for as long as possible using novel anti-cancer medicines either as monotherapy or in combination with already approved agents.”

VHIO’s Breast Cancer Group has also succeeded in establishing itself as one of the most active and renowned in Europe through its deeply rooted collaboration with additional VHIO groups including our Growth Factors, Experimental Therapeutics, Tumor Immunology & Immunotherapy, and Hereditary Cancer Genetics Groups, directed by Joaquin Arribas, Violeta Serra, Alena Gros, and Judith Balmaña respectively, as well as several other breast cancer professionals and specialties across the Vall d’Hebron Barcelona Hospital Campus.

 “It is thanks to VHIO’s purely translational and multidisciplinary research model and connective team work, that we can more swiftly apply cancer discovery driven by preclinical and translational science of excellence to guide the clinical development of more effective, potent and precise treatment approaches against several tumor types including breast cancer,” added Josep Tabernero, VHIO’s Director.

He continued,VHIO’s direct access to cancer patients is central to our purely translational research model. Located within the Vall d’Hebron Barcelona Hospital Campus, HUVH affords our Institute essential proximity to patients as well as the entire spectrum of oncology professionals who care for them.”

Based on the molecular measurement and make-up of each tumor, the specificities of each individual’s disease, some patients with advanced disease may be enrolled in combinatorial studies that are designed to overcome mechanisms of resistance with different agents combined with chemotherapy, endocrine therapy, or CDK4/6 and PARP inhibitors. “Crucially, our research, in partnership with many leading experts across the globe, has led to the market approval of several more effective anti-cancer medicines that have improved outcomes for countless breast cancer patients globally,” said Cristina.

Concerning CDK4/6 inhibitors, Cristina’s Group has significantly contributed to the development of these promising contenders, either as monotherapy or in combination. Meritxell Bellet, Medical Oncologist and Clinical Investigator in the same group, has not only developed and led many of these clinical trials but also closely collaborated with Violeta Serra’s team to more effectively tackling resistance to CDK4/6, as well as AR modulators (SARMS) in breast tumors.

Reflective of Meritxell’s particular expertise in the clinical management of the former, she recently first authored a consensus paper* to help steer the daily practice of oncologists dealing with these agents. This go-to guide, formulated based on the findings and highlights presented at the First Workshop on Pharmacology and Management of Cyclin-dependent kinase 4/6 inhibitors: Consensus about Concomitant Medications, promoted by the Spanish Breast Cancer Cooperative Group (SOLTI).

The development of CDK4/6 inhibitors has undeniably led to an important shift in the therapeutic management of HR+ metastatic breast cancer, but much work still needs to be done in order to better decipher the mechanisms that govern resistance in these patients. Current research centers on novel strategies to overcome disease progression and further improve outcomes for these patients.

Similarly, while PARPi are now delivering on their promise in the clinic, efforts must continue to more precisely predict which patients would be most likely to respond to these treatments. VHIO is not only leading research aimed at identifying clinical biomarkers of sensitivity to PARPi  towards a more informed patient selection matched to these therapies through its CaixaImpulse PARPiPRED project but also pioneering studies to establish mechanisms of resistance and assess drug-drug combinations tested preclinically in PDX models. These preclinical and translational efforts are led by Violeta Serra’s Experimental Therapeutics Group with the combined expertise of Judith Balmaña’s Hereditary Cancer Genetics Group and Cristina Saura’s team.

As we embark on our second decade, we can and will only continue to deliver on the promise of precision medicine against breast cancer through the generous support that we receive from our treasured institutional supporters, international and national public funding, private institutions, companies, charitable endeavors, and individual donors. Only through this strong backing and belief in our research will the clock continue to tick in our favor – against cancer,” concluded Cristina.

The many successes over the past decade have also been possible thanks to the investments championed by the FERO Foundation, one of VHIO’s private patrons. This support spurred the building of our internationally renowned Breast Cancer Center. Located on two floors of our Hospital’s Maternity and Pediatrics Building our Breast Cancer Center Endavant I de Cara (loosely translated as ‘upwards, head high’, was financed through a personal donation received from Maria Angels Sanahuja, in memorium of Roman Sanahuja and Francisca Pons.

Dedicated to advancing the prevention, treatment and care of breast cancer patients by pooling and combining expertise across all specialties in multidisciplinary teams, our Center houses the entire circuit of patient care incorporating all the necessary services and spaces including consultancy rooms, screening facilities and technologies, radiomics, cutting edge diagnostics, and pharmacy.

To discover more about VHIO’s research lines and projects aimed at advancing breast cancer discovery, treatment and care please contact Amanda Wren, Director of Communications at VHIO, via email: awren@vhio.net.

Reference:

* Meritxell Bellet, Faten Ahmad, Rafael Villanueva, Carolina Valdivia, Julián Palomino-Doza, Ada Ruiz, Xavier Gonzàlez, Encarna Adrover, Analía Azaro, Maria Valls-Margarit, Josep Lluís Parra, Juan Aguilar, Maria Vidal, Anastasi Martín, Joaquín Gavilá, Santiago Escrivá-de-Romaní, Antonia Perelló, Cristina Hernando, Ainhara Lahuerta, Pilar Zamora, Victoria Reyes, María Alcalde, Helena Masanas, Pamela Céliz, Isabel Ruíz, Miguel Gil, Miguel Àngel Seguí, and Lorena de la Peña. Palbociclib and ribociclib in breast cancer: consensus workshop on the management of concomitant medication. Ther Adv Med Oncol. 2019; 11: 1758835919833867.

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