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Article ; Online: Clinical trial data and emerging strategies: HER2-positive breast cancer.

Pernas, Sonia / Tolaney, Sara M

2022 Volume 193, Issue 2, Page(s) 281–291

Abstract: A deeper insight into tumor biology and HER2 signaling has led to the development of novel anti-HER2 drugs that have significantly improved the prognosis of patients with HER2-positive breast cancer. The breast cancer immune microenvironment has emerged ... ...

Abstract	A deeper insight into tumor biology and HER2 signaling has led to the development of novel anti-HER2 drugs that have significantly improved the prognosis of patients with HER2-positive breast cancer. The breast cancer immune microenvironment has emerged as a potential prognostic factor. Moreover, the host immune system not only seems to play a critical role in the prognosis of HER2-positive breast cancer, but also seems to modulate treatment response to some HER2-targeted agents. Here, we review the latest evidence of the role of immunotherapy in HER2-positive breast cancer and present emerging strategies.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Female ; Humans ; Immunotherapy ; Lymphocytes, Tumor-Infiltrating ; Prognosis ; Receptor, ErbB-2 ; Tumor Microenvironment
Chemical Substances	Antineoplastic Agents ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2022-04-09
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	604563-7
ISSN	1573-7217 ; 0167-6806
ISSN (online)	1573-7217
ISSN	0167-6806
DOI	10.1007/s10549-022-06575-7
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Zs.A 1655: Show issues

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Article ; Online: Management of Early-Stage Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer.

Pernas, Sonia / Tolaney, Sara M

JCO oncology practice

2021 Volume 17, Issue 6, Page(s) 320–330

Abstract: The addition of trastuzumab to chemotherapy dramatically improved the prognosis of early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, 15%-31% of patients still develop disease recurrence, on the basis of long- ... ...

Abstract	The addition of trastuzumab to chemotherapy dramatically improved the prognosis of early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, 15%-31% of patients still develop disease recurrence, on the basis of long-term follow-up of adjuvant pivotal trials. A better understanding of tumor biology has led to the development of optimized anti-HER2 drugs and add-on strategies to further improve survival outcomes. In the neoadjuvant setting, dual HER2 blockade with trastuzumab and pertuzumab plus chemotherapy has increased the rate of pathologic complete response, a surrogate marker of improved long-term outcome; yet, in the adjuvant setting, it has led to small benefits in invasive disease-free survival. Extended adjuvant therapy with the irreversible pan-HER2 inhibitor neratinib is an option for selected patients with HER2-positive and estrogen receptor-positive disease who have received neoadjuvant or adjuvant chemotherapy plus trastuzumab. Additionally, the use of the antibody-drug conjugate trastuzumab-emtansine has led to a significant improvement in invasive disease-free survival for patients with residual disease following neoadjuvant therapy and has taught us the importance of using preoperative therapy to adapt adjuvant treatment. Nevertheless, recurrences in the brain remain an important caveat, and not all patients benefit to the same extent from anti-HER2 therapies. Biologic heterogeneity within HER2-positive disease may modulate treatment response and prognosis. De-escalating treatment strategies to avoid unnecessary treatments and toxicities, without compromising outcomes, have become a crucial focus of research. To stratify patient risks and optimize treatment selection, other biomarkers including intrinsic subtype, level of HER2, and tumor-infiltrating lymphocytes should be further evaluated. We discuss the latest evidence on the current approach of early-stage, HER2-positive breast cancer and present future perspectives on its management.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/drug therapy ; Female ; Humans ; Neoplasm Recurrence, Local ; Receptor, ErbB-2/therapeutic use
Chemical Substances	ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2021-06-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	3028198-2
ISSN	2688-1535 ; 2688-1527
ISSN (online)	2688-1535
ISSN	2688-1527
DOI	10.1200/OP.21.00020
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Article ; Online: Immune Checkpoint Inhibitors and Novel Immunotherapy Approaches for Breast Cancer.

Cejuela, Mónica / Vethencourt, Andrea / Pernas, Sonia

Current oncology reports

2022 Volume 24, Issue 12, Page(s) 1801–1819

Abstract: Purpose of review: To critically review the existing evidence on immune checkpoint inhibitors (ICIs) in early-stage and metastatic breast cancer and discuss emerging strategies in the different breast cancer subtypes.: Recent findings: Immunotherapy ... ...

Abstract	Purpose of review: To critically review the existing evidence on immune checkpoint inhibitors (ICIs) in early-stage and metastatic breast cancer and discuss emerging strategies in the different breast cancer subtypes. Recent findings: Immunotherapy has become one of the major milestones in contemporary oncology, revolutionizing the treatment of multiple solid tumors. ICI agents combined with chemotherapy have demonstrated significant efficacy in both early-stage and metastatic triple-negative breast cancer. However, only a subgroup of patients responds to those agents and some associated toxicities, although infrequent, can be life-disabling. Emerging data from immunotherapy studies in advanced hormone receptor-positive (HR +) breast cancer as well as HER2-positive disease are arising with mixed results. Although breast cancer has not classically been considered a hot tumor, ICIs have proven to be effective in a subset of breast cancer patients. However, much remains to be learned, and the identification of new biomarkers beyond PD-L1 expression is essential not only to improve the efficacy of ICI but also to identify patients who can avoid them, together with their toxicities and costs.
MeSH term(s)	Humans ; Immune Checkpoint Inhibitors/therapeutic use ; B7-H1 Antigen ; Immunotherapy/methods ; Triple Negative Breast Neoplasms ; Immunologic Factors
Chemical Substances	Immune Checkpoint Inhibitors ; B7-H1 Antigen ; Immunologic Factors
Language	English
Publishing date	2022-10-18
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2057359-5
ISSN	1534-6269 ; 1523-3790
ISSN (online)	1534-6269
ISSN	1523-3790
DOI	10.1007/s11912-022-01339-4
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Zs.A 5521: Show issues

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Article ; Online: Targeting HER2 heterogeneity in early-stage breast cancer.

Pernas, Sonia / Tolaney, Sara M

Current opinion in oncology

2020 Volume 32, Issue 6, Page(s) 545–554

Abstract: Purpose of review: HER2-positive (HER2+) breast cancer is clinically and biologically a heterogenous disease and not all patients benefit to the same extent from current anti-HER2 therapies.: Recent findings: Among HER2+ breast cancer, molecular ... ...

Abstract	Purpose of review: HER2-positive (HER2+) breast cancer is clinically and biologically a heterogenous disease and not all patients benefit to the same extent from current anti-HER2 therapies. Recent findings: Among HER2+ breast cancer, molecular intrinsic subtypes, PIK3CA mutation status, levels of HER2 gene/protein, immune infiltration, or intratumor heterogeneity modulate HER2-treatment sensitivity. HER2-enriched carcinomas, with high levels of HER2 and tumor-infiltrating lymphocytes (TILs) are highly sensitive to anti-HER2 therapies, regardless of chemotherapy. Luminal A/B tumors are more estrogen receptor-dependent than HER2-dependent, harbor higher rates of PIK3CA mutations, and are less responsive to anti-HER2 treatment. HER2 intratumoral heterogeneity that exists in approximately 10% of HER2+ disease may also cause treatment resistance. Early changes occur during neoadjuvant anti-HER2 therapy that can predict response. Importantly, HER2 expression is not a binary but rather a continuous variable. Overall, 34-63% of HER2-negative breast cancers express HER2, and HER2-low tumors have become a new entity, for which novel targeted therapies may be effective. Summary: Although much of what is discussed currently remains investigational, it is clear that HER2+ breast cancer is a complex disease comprising different entities. Future strategies to escalate or de-escalate treatment in early-stage HER2+ disease should consider other biomarkers beyond HER2 and estrogen receptor status, including intrinsic subtype, HER2 levels, and TILs; and evaluate different treatment strategies among patients with estrogen receptor-positive/HER2+ and estrogen receptor-negative/HER2+ diseases.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy ; Breast Neoplasms/immunology ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Clinical Trials, Phase II as Topic ; Clinical Trials, Phase III as Topic ; Female ; Humans ; Lymphocytes, Tumor-Infiltrating/immunology ; Neoplasm Staging ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Randomized Controlled Trials as Topic ; Receptor, ErbB-2/antagonists & inhibitors ; Receptor, ErbB-2/metabolism
Chemical Substances	Antineoplastic Agents ; Protein Kinase Inhibitors ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2020-09-14
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1049384-0
ISSN	1531-703X ; 1040-8746
ISSN (online)	1531-703X
ISSN	1040-8746
DOI	10.1097/CCO.0000000000000685
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Zs.A 3046: Show issues

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Article: HER2-positive breast cancer: new therapeutic frontiers and overcoming resistance.

Pernas, Sonia / Tolaney, Sara M

Therapeutic advances in medical oncology

2019 Volume 11, Page(s) 1758835919833519

Abstract: The introduction of anti-HER2 therapies to the treatment of patients with HER2-positive breast cancer has led to dramatic improvements in survival in both early and advanced settings. Despite this breakthrough, nearly all patients with metastatic HER2- ... ...

Abstract	The introduction of anti-HER2 therapies to the treatment of patients with HER2-positive breast cancer has led to dramatic improvements in survival in both early and advanced settings. Despite this breakthrough, nearly all patients with metastatic HER2-positive breast cancer eventually progress on anti-HER2 therapy due to
Language	English
Publishing date	2019-03-19
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2503443-1
ISSN	1758-8359 ; 1758-8340
ISSN (online)	1758-8359
ISSN	1758-8340
DOI	10.1177/1758835919833519
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Article: Lights and Shadows in Immuno-Oncology Drug Development.

Bergamino Sirvén, Milana / Pernas, Sonia / Cheang, Maggie C U

Cancers

2021 Volume 13, Issue 4

Abstract: The rapidly evolving landscape of immuno-oncology (IO) is redefining the treatment of a number of cancer types. IO treatments are becoming increasingly complex, with different types of drugs emerging beyond checkpoint inhibitors. However, many of the new ...

Abstract	The rapidly evolving landscape of immuno-oncology (IO) is redefining the treatment of a number of cancer types. IO treatments are becoming increasingly complex, with different types of drugs emerging beyond checkpoint inhibitors. However, many of the new drugs either do not progress from phase I-II clinical trials or even fail in late-phase trials. We have identified at least five areas in the development of promising IO treatments that should be redefined for more efficient designs and accelerated approvals. Here we review those critical aspects of IO drug development that could be optimized for more successful outcome rates in all cancer types. It is important to focus our efforts on the mechanisms of action, types of response and adverse events of these novel agents. The use of appropriate clinical trial designs with robust biomarkers of response and surrogate endpoints will undoubtedly facilitate the development and subsequent approval of these drugs. Further research is also needed to establish biomarker-driven strategies to select which patients may benefit from immunotherapy and identify potential mechanisms of resistance.
Language	English
Publishing date	2021-02-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13040691
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Article ; Online: Metformin and Breast Cancer: Where Are We Now?

Cejuela, Mónica / Martin-Castillo, Begoña / Menendez, Javier A / Pernas, Sonia

International journal of molecular sciences

2022 Volume 23, Issue 5

Abstract: Breast cancer is the most prevalent cancer and the leading cause of cancer-related death among women worldwide. Type 2 diabetes-associated metabolic traits such as hyperglycemia, hyperinsulinemia, inflammation, oxidative stress, and obesity are well- ... ...

Abstract	Breast cancer is the most prevalent cancer and the leading cause of cancer-related death among women worldwide. Type 2 diabetes-associated metabolic traits such as hyperglycemia, hyperinsulinemia, inflammation, oxidative stress, and obesity are well-known risk factors for breast cancer. The insulin sensitizer metformin, one of the most prescribed oral antidiabetic drugs, has been suggested to function as an antitumoral agent, based on epidemiological and retrospective clinical data as well as preclinical studies showing an antiproliferative effect in cultured breast cancer cells and animal models. These benefits provided a strong rationale to study the effects of metformin in routine clinical care of breast cancer patients. However, the initial enthusiasm was tempered after disappointing results in randomized controlled trials, particularly in the metastatic setting. Here, we revisit the current state of the art of metformin mechanisms of action, critically review past and current metformin-based clinical trials, and briefly discuss future perspectives on how to incorporate metformin into the oncologist's armamentarium for the prevention and treatment of breast cancer.
MeSH term(s)	Animals ; Breast Neoplasms/prevention & control ; Diabetes Mellitus, Type 2/chemically induced ; Diabetes Mellitus, Type 2/drug therapy ; Female ; Humans ; Hypoglycemic Agents/adverse effects ; Metformin/pharmacology ; Metformin/therapeutic use ; Retrospective Studies
Chemical Substances	Hypoglycemic Agents ; Metformin (9100L32L2N)
Language	English
Publishing date	2022-02-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23052705
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Article ; Online: Metformin and Breast Cancer

Mónica Cejuela / Begoña Martin-Castillo / Javier A. Menendez / Sonia Pernas

International Journal of Molecular Sciences, Vol 23, Iss 2705, p

Where Are We Now?

2022 Volume 2705

Abstract: Breast cancer is the most prevalent cancer and the leading cause of cancer-related death among women worldwide. Type 2 diabetes–associated metabolic traits such as hyperglycemia, hyperinsulinemia, inflammation, oxidative stress, and obesity are well- ... ...

Abstract	Breast cancer is the most prevalent cancer and the leading cause of cancer-related death among women worldwide. Type 2 diabetes–associated metabolic traits such as hyperglycemia, hyperinsulinemia, inflammation, oxidative stress, and obesity are well-known risk factors for breast cancer. The insulin sensitizer metformin, one of the most prescribed oral antidiabetic drugs, has been suggested to function as an antitumoral agent, based on epidemiological and retrospective clinical data as well as preclinical studies showing an antiproliferative effect in cultured breast cancer cells and animal models. These benefits provided a strong rationale to study the effects of metformin in routine clinical care of breast cancer patients. However, the initial enthusiasm was tempered after disappointing results in randomized controlled trials, particularly in the metastatic setting. Here, we revisit the current state of the art of metformin mechanisms of action, critically review past and current metformin-based clinical trials, and briefly discuss future perspectives on how to incorporate metformin into the oncologist’s armamentarium for the prevention and treatment of breast cancer.
Keywords	metformin ; breast cancer ; diabetes ; insulin ; clinical trials ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610 ; 616
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Elderly patients with hormone receptor-positive HER2-negative metastatic breast cancer treated with CDK4/6 inhibitors in a multicentre cohort.

Pla, Helena / Felip, Eudald / Obadia, Verónica / Pernas, Sonia / Viñas, Gemma / Margelí, Mireia / Fort-Culillas, Roser / Del Barco, Sonia / Sabaté, Nuria / Fort, Eduard / Lezcano, Clara / Cirauqui, Beatriz / Quiroga, Vanesa / Stradella, Agostina / Gil Gil, Miguel / Esteve, Anna / Recalde, Sabela

Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico

2024

Abstract: Introduction: Cyclin-dependent kinases 4/6 inhibitors (CDK 4/6i) combined with endocrine therapy have become the gold standard in hormone receptor-positive (HR +) HER2-negative (HER2-) metastatic breast cancer (MBC). However, there is a significant lack ...

Abstract	Introduction: Cyclin-dependent kinases 4/6 inhibitors (CDK 4/6i) combined with endocrine therapy have become the gold standard in hormone receptor-positive (HR +) HER2-negative (HER2-) metastatic breast cancer (MBC). However, there is a significant lack of data regarding the efficacy and safety of these treatments in elderly patients. We present the results of a real-world data (RWD) cohort stratified by age at treatment initiation (≥ 70 years compared to patients < 70 years). Methods: Clinico-pathological data of HR + HER2- MBC patients who were candidates for CDK4/6i therapy between January 2017 and December 2020 at the Institut Català d'Oncologia (Spain) were retrospectively collected. The primary goal was to assess Progression-Free Survival (PFS), Overall Survival (OS), and safety outcomes within this patient population. Results: A total of 274 patients with MBC who received CDK4/6i treatment were included in the study. Among them, 84 patients (30.8%) were aged ≥ 70 years, with a mean age of 75, while 190 patients (69.2%) were under the age of 70, with a mean age of 55.7 years. The most frequently observed grade 3-4 toxicity was neutropenia, with similar rates in both the < 70 group (43.9%) and the ≥ 70 group (47.9%) (p = 0.728). The median Progression-Free Survival (mPFS) for the first-line CDK4/6i treatment was 22 months (95% CI, 15.4-39.8) in the < 70 group and 20.8 months (95% CI 11.2-NR) in the ≥ 70 group (p = 0.67). Similarly, the median PFS for the second-line CDK4/6i treatment was 10.4 months (95% CI, 7.4-15.1) and 7.1 months (95% CI 4.4-21.3) (p = 0.79), respectively. Median overall survival (mOS) was not reached either for the first- and second-line treatment. Conclusions: Our RWD suggests that elderly patients, when compared to those under 70, experience similar survival outcomes and exhibit comparable tolerance for CDK4/6i therapy.
Language	English
Publishing date	2024-03-22
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2397359-6
ISSN	1699-3055 ; 1699-048X
ISSN (online)	1699-3055
ISSN	1699-048X
DOI	10.1007/s12094-024-03399-3
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Zs.A 6644: Show issues

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Article ; Online: Bull Semen Obtained on Beef Farms by Electroejaculation: Sperm Quality in the First Two Hours of Storing with Different Extenders and Holding Temperatures

Pernas, Santiago / Fernandez-Novo, Aitor / Barrajon-Masa, Clara / Mozas, Patricia / Pérez-Villalobos, Natividad / Martín-Maldonado, Bárbara / Oliet, Agustín / Astiz, Susana / Pérez-Garnelo, Sonia S.

Animals. 2023 May 06, v. 13, no. 9

2023

Abstract: Sperm quality decreases over time, so bull semen may need to be preserved after field collection. However, the effect of handling such semen samples from commercial farms and placing them in very short–term storage has not been elucidated. Therefore, ... ...

Abstract	Sperm quality decreases over time, so bull semen may need to be preserved after field collection. However, the effect of handling such semen samples from commercial farms and placing them in very short–term storage has not been elucidated. Therefore, ejaculate from 25 bulls from 1 dairy and 14 beef cattle farms were collected under farm conditions and evaluated for semen quality during the first two hours after collection. Two commercial extenders (AndroMed® and BIOXcell®) and two different storage temperatures (5 °C and room temperature) were used to evaluate the influence on semen quality and sperm kinetics in ejaculates grouped into three evaluation times, based on time since collection (Time 1: <75 min, n = 7; Time 2: 75–105 min, n = 11; and Time 3: 105–120 min, n = 7). Classical semen parameters, sperm motion kinetics by CASA and colony-forming units were assessed. The differences between both extenders in curvilinear and straight–line velocities (VCL and VSL) for the different time groups (Time 2 and Time 3) were statistically significant for p < 0.05. AndroMed® showed lower VSL, straightness and linearity in sperm compared to BIOXcell® (p < 0.05). In conclusion, AndroMed® induced more curvilinear movement, while BIOXcell® stimulated straighter motility.
Keywords	ambient temperature ; beef ; beef cattle ; farms ; semen quality ; sperm quality ; storage time
Language	English
Dates of publication	2023-0506
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2606558-7
ISSN	2076-2615
ISSN	2076-2615
DOI	10.3390/ani13091561
Database	NAL-Catalogue (AGRICOLA)

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