Exploring the Interplay between BRCA Mutations and Hormonal Pathways in Triple-Negative Breast Cancer

*Rashika Rajput, ¹Khushi Gupta
*Researcher Scientist, Laureate Institute of Pharmacy
¹Research Scholar, Laureate Institute of Pharmacy

Article Details

Title: Exploring the Interplay between BRCA Mutations and Hormonal Pathways in Triple-Negative Breast Cancer

Authors: Rashika Rajput, Khushi Gupta

Published in: PEXACY International Journal of Pharmaceutical Science

Volume/Issue: 2(12)

Pages: 186-205

Publication Date: 09/12/2023

DOI: 10.5281/zenodo.10315793

ISSN: 2584-024X

Language: English

Publisher: PEXACY International Journal of Pharmaceutical Science

PDF Download: Access Full Paper

Abstract: This review comprehensively explores the management of BRCA-mutated triple-negative breast cancer (TNBC), emphasizing the critical roles of genetic counseling, personalized treatment strategies, psychosocial support, and vigilant surveillance. It delves into the challenges of BRCA mutations in TNBC, including the psychological impact, treatment complexities, and the necessity for tailored surveillance and risk reduction strategies. The review highlights the advancements in targeted therapies, particularly PARP inhibitors, and the importance of a multidisciplinary approach to address the diverse needs of patients. It underscores the need for ongoing research and collaboration among healthcare professionals to improve prognosis and quality of life for patients with this aggressive cancer subtype. Psychosocial support is identified as a key component of comprehensive care, addressing the significant emotional and psychological burden faced by patients with BRCA-mutated TNBC. The review discusses the need for robust support systems, including psychological counseling and patient education, to help patients cope with the diagnosis and its implications. In conclusion, the review underscores the complexities of managing BRCA-mutated TNBC and the importance of a multifaceted approach that integrates genetic counseling, personalized medicine, psychosocial support, and vigilant surveillance.

Keywords: BRCA Mutations, Triple-Negative Breast Cancer, Genetic Counseling, Personalized Treatment, Psychosocial Support, Surveillance Strategies, PARP Inhibitors, Drug Resistance, Prophylactic Measures, Multidisciplinary Approach.
Article can be accessed online on: PEXACY International Journal of Pharmaceutical Science
DOI: 10.5281/zenodo.10315793
Corresponding Author- *Rashika Rajput
Update: Received on 05/11/2023; Accepted; 06/12/2023, Published on; 09/12/2023

INTRODUCTION

Triple-negative breast cancer (TNBC) represents a particularly aggressive and challenging subtype of breast cancer, characterized by the absence of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2) expression. This subtype is notorious for its poor prognosis and limited treatment options, primarily due to its heterogeneity and complex molecular profile. A critical area of research in TNBC is understanding the interplay between BRCA mutations and hormonal pathways, which could unlock new avenues for targeted therapies and improve patient outcomes.

BRCA1 and BRCA2 genes are pivotal in DNA repair mechanisms, and mutations in these genes are known to significantly increase the risk of developing breast cancer, including TNBC. Recent studies, such as those by Drewett et al. (2022), have focused on evaluating the efficacy of PARP inhibitors like Olaparib in patients with BRCA-mutated TNBC, revealing promising therapeutic potentials. The PARTNER trial, for instance, is a notable study that investigates the addition of Olaparib to platinum-based neoadjuvant chemotherapy in patients with germline BRCA-mutated TNBC, aiming to enhance treatment efficacy and patient survival (L. Drewett, Pinilla, et al., 2022; L. Drewett, Lucey, et al., 2022).

Moreover, the role of hormonal pathways in TNBC, particularly in the context of BRCA mutations, is an area of growing interest. While TNBC is traditionally defined by the lack of hormone receptor expression, emerging research suggests that hormonal factors may still play a role in its pathogenesis and progression. For example, studies like those by Masoud et al. (2021) have explored the clinicopathological characteristics and androgen receptor expression in TNBC, providing insights into potential hormonal influences even in the absence of traditional hormone receptors.

The complexity of TNBC is further highlighted by the exploration of diverse molecular pathways and therapeutic targets linked to this cancer subtype. Mustafa et al. (2023) delve into the molecular pathways and therapeutic targets in TNBC, underscoring the importance of understanding the intricate molecular mechanisms driving this disease for the development of effective treatments.

In addition, the integration of multiomics approaches in TNBC research, as discussed by Martini et al. (2023), is crucial for identifying specific mechanisms and potential therapeutic targets, especially in the context of genetic and racial disparities. This approach is essential for tailoring treatments to individual patient profiles, thereby enhancing the efficacy of therapeutic interventions.

In conclusion, the exploration of the interplay between BRCA mutations and hormonal pathways in TNBC opens new horizons for understanding the disease’s molecular underpinnings and developing more effective, personalized treatment strategies. This research is pivotal in addressing the challenges posed by TNBC and improving the prognosis for patients affected by this aggressive cancer subtype.

THERAPEUTIC STRATEGIES IN BRCA-MUTATED TRIPLE-NEGATIVE BREAST CANCER

Emerging Treatment Approaches and Clinical Implications

Triple-negative breast cancer (TNBC), particularly with BRCA mutations, presents unique challenges in treatment due to its aggressive nature and lack of hormone receptor targets. Recent advancements in therapeutic strategies have focused on exploiting the genetic vulnerabilities of BRCA-mutated TNBC, offering new hope for effective treatments.

PARP Inhibitors and Combination Therapies

The use of PARP inhibitors, such as Olaparib, has emerged as a promising strategy for BRCA-mutated TNBC. Studies like those by Guney Eskiler et al. (2023) have explored novel combination treatments of CDK 4/6 inhibitors with PARP inhibitors, showing enhanced efficacy in TNBC cells. This approach leverages the concept of synthetic lethality, targeting the compromised DNA repair mechanisms in BRCA-mutated cells. Güney Eski̇ler et al. (2020) have also investigated the reversal effect of quercetin on talazoparib resistance in BRCA1 mutant TNBC, suggesting potential ways to overcome drug resistance.

Neoadjuvant Treatment Regimens

Neoadjuvant treatment regimens in BRCA-mutated TNBC have been a focus of several studies. Caramelo et al. (2022) conducted a systematic review and meta-analysis to evaluate the efficacy of different neoadjuvant treatment regimens in this subgroup, providing valuable insights into optimizing pre-surgical therapy. Their findings underscore the importance of tailoring neoadjuvant treatments to the specific genetic makeup of the tumor.

Targeting Molecular Pathways

The molecular subtypes of TNBC, as discussed by Lehmann et al. (2015), have significant implications for therapy, with different subtypes responding variably to treatment modalities. Understanding these subtypes is crucial for developing targeted therapies. Medina et al. (2020) reviewed conventional and advanced therapeutic strategies in TNBC, highlighting the need for a deeper understanding of the disease’s molecular pathways for effective treatment.

Overcoming Drug Resistance

The issue of drug resistance in BRCA-mutated TNBC is a significant challenge. Bustos et al. (2023) explored the role of miR-181a in driving PARP inhibitor resistance in BRCA-mutated TNBC and ovarian cancer, suggesting new targets to overcome resistance. Similarly, Fang et al. (2023) developed a progressively disassembled DNA repair inhibitors nanosystem for treating BRCA wild-type TNBC, indicating the potential of nanomedicine in addressing drug resistance.

Future Directions

Kumari et al. (2023) discussed emerging targeted therapeutic strategies for the treatment of TNBC, emphasizing the need for ongoing research and development of novel treatment approaches. The evolving landscape of TNBC therapy, particularly for BRCA-mutated subtypes, requires continuous innovation and clinical trials to validate new treatment strategies.

In conclusion, the therapeutic landscape for BRCA-mutated TNBC is rapidly evolving, with a focus on exploiting genetic vulnerabilities, developing combination therapies, and overcoming drug resistance. Continued research and clinical trials are essential for translating these advancements into effective treatment options for patients with this challenging subtype of breast cancer.

IMMUNOTHERAPY IN BRCA-MUTATED TRIPLE-NEGATIVE BREAST CANCER

Advancements and Clinical Outcomes

Triple-negative breast cancer (TNBC) with BRCA mutations presents a unique challenge in cancer therapy due to its aggressive nature and lack of hormone receptors. Immunotherapy has emerged as a promising treatment modality, offering new hope for patients with this subtype of breast cancer.

Immunotherapy and PARP Inhibitors

The integration of immunotherapy with PARP inhibitors is a novel approach in treating BRCA-mutated TNBC. Caputo et al. (2023) reported a case of long-term complete response with third-line PARP inhibitor after immunotherapy in a patient with TNBC, highlighting the potential synergistic effect of these therapies. This combination aims to enhance the immune response while targeting the DNA repair deficiencies inherent in BRCA-mutated cells.

PD-L1 Inhibitors and Antiangiogenic Drugs

The role of PD-L1 inhibitors in TNBC, particularly in combination with antiangiogenic drugs, is an area of active research. Li et al. (2023) investigated the combined effect and mechanism of antiangiogenic drugs and PD-L1 inhibitors on cell apoptosis in TNBC, providing insights into the potential mechanisms of action and therapeutic benefits of this combination.

Metformin and PARP Inhibitors

Han et al. (2019) explored the reversal effect of metformin on PARP inhibitors-induced epithelial-mesenchymal transition and PD-L1 upregulation in TNBC. This study suggests that metformin could potentially enhance the efficacy of PARP inhibitors and immunotherapy in TNBC, particularly in BRCA-mutated cases.

Neoadjuvant Immunotherapy

Neoadjuvant immunotherapy regimens are being evaluated for their efficacy in BRCA-mutated TNBC. Caramelo et al. (2022) conducted a systematic review and meta-analysis on different neoadjuvant treatment regimens, including immunotherapy, in this subgroup. Their findings are crucial for determining the most effective pre-surgical treatment strategies.

Future Perspectives

Desai and Tan (2023) discussed targeted therapies and the evolving standard of care for TNBC and germline BRCA1/2-mutated breast cancers in the high-risk, early-stage setting. The study emphasizes the importance of ongoing research and clinical trials to establish the most effective immunotherapy-based treatment regimens for these patients.

In conclusion, immunotherapy represents a significant advancement in the treatment of BRCA-mutated TNBC. The combination of immunotherapy with PARP inhibitors, the exploration of PD-L1 inhibitors with antiangiogenic drugs, and the potential role of metformin in enhancing treatment efficacy are promising developments. Ongoing research and clinical trials are essential to fully understand the benefits and optimize the use of immunotherapy in this challenging breast cancer subtype.

THE ROLE OF GENETIC COUNSELING IN BRCA-MUTATED TRIPLE-NEGATIVE BREAST CANCER

Navigating the Genetic Landscape for Optimal Patient Care

The integration of genetic counseling in the management of BRCA-mutated triple-negative breast cancer (TNBC) is crucial for providing comprehensive patient care. This approach not only aids in risk assessment and decision-making but also supports patients and their families in understanding the implications of genetic mutations on treatment and prevention strategies.

Importance of Genetic Testing and Counseling

Genetic testing for BRCA mutations has become an integral part of managing breast cancer, particularly in TNBC. Alvarado-Muñoz et al. (2023) highlighted the prevalence of BRCA1/2 gene mutations in patients with high-risk breast cancer, emphasizing the need for genetic counseling in these cases. Ahmed et al. (2018) discussed the barriers and opportunities in genetic testing for BRCA gene mutations in Europe, underscoring the strategic policy response required to support at-risk women and families.

Counseling in Treatment Decision-Making

Genetic counseling plays a pivotal role in guiding treatment decisions, especially in the context of emerging therapies like PARP inhibitors. Cortesi et al. (2021) provided an overview of PARP inhibitors for the treatment of breast cancer, where the presence of BRCA mutations significantly influences treatment choices. The role of genetic counselors in explaining the implications of these targeted therapies is vital for informed decision-making.

Prophylactic Measures and Risk Reduction

For BRCA mutation carriers, prophylactic measures such as bilateral prophylactic mastectomy can be a consideration. Franceschini et al. (2019) discussed the aspects that surgeons need to know about this procedure in BRCA mutation carriers, highlighting the importance of genetic counseling in discussing these risk-reducing options.

Mainstreaming Genetic Counseling

The mainstreaming of genetic counseling into oncology clinics, as discussed by Verma et al. (2019), is crucial for the effective management of BRCA-mutated TNBC. This approach ensures that patients receive timely and appropriate genetic counseling, which is essential for understanding their risk and making informed choices about their treatment and prevention strategies.

Addressing Disparities in Genetic Counseling

Martini et al. (2023) emphasized the importance of addressing disparities in genetic counseling, particularly in identifying specific mechanisms in diverse populations with TNBC. This approach is crucial for ensuring equitable access to genetic counseling and personalized care.

In conclusion, genetic counseling is an indispensable component in the management of BRCA-mutated TNBC. It plays a critical role in risk assessment, guiding treatment decisions, discussing prophylactic measures, and supporting patients and their families. Ensuring access to genetic counseling and addressing disparities in this service are essential for providing optimal care to patients with TNBC.

PSYCHOSOCIAL IMPACT OF BRCA MUTATIONS IN TRIPLE-NEGATIVE BREAST CANCER PATIENTS

Understanding the Emotional and Social Challenges

The diagnosis of triple-negative breast cancer (TNBC) with BRCA mutations not only presents clinical challenges but also has profound psychosocial implications for patients. Understanding the emotional, psychological, and social impact of this diagnosis is crucial for providing comprehensive care and support.

Emotional and Psychological Burden

The discovery of a BRCA mutation in TNBC patients can lead to significant emotional and psychological distress. Kihn-Alarcón et al. (2023) highlighted the prevalence of BRCA mutations in TNBC patients, which can evoke feelings of fear, anxiety, and uncertainty about the future. The psychological burden associated with the increased risk of cancer recurrence and the potential impact on family members necessitates effective psychosocial support and counseling.

Social and Familial Implications

The identification of BRCA mutations has important implications for family members, as it raises concerns about the hereditary nature of the risk. Paris et al. (2020) discussed the impact of BRCA mutations on treatment outcomes in TNBC, which can also influence family dynamics and decision-making regarding genetic testing and preventive measures. The role of genetic counselors in navigating these complex family discussions is vital.

Fertility and Reproductive Concerns

For many TNBC patients with BRCA mutations, fertility and reproductive health become significant concerns. Kim et al. (2022) explored the impact of BRCA mutations and hormone receptor status on the reproductive potential of breast cancer patients undergoing fertility preservation. Addressing these concerns is essential for supporting patients in their reproductive choices and planning.

Coping Strategies and Support Systems

Developing effective coping strategies and support systems is crucial for TNBC patients with BRCA mutations. Pogoda et al. (2020) examined the effects of BRCA germline mutations on TNBC prognosis, highlighting the need for psychological support to help patients cope with the diagnosis and its implications. Support groups, counseling, and patient education play a key role in providing this support.

Impact on Treatment Decisions

The presence of BRCA mutations can significantly impact treatment decisions, including considerations for prophylactic surgeries and targeted therapies. Lin et al. (2022) investigated the impact of BRCA mutations on survival and the risk of contralateral breast cancer, emphasizing the importance of informed decision-making in the management of TNBC.

In conclusion, the psychosocial impact of BRCA mutations in TNBC patients is multifaceted, encompassing emotional, psychological, social, and familial aspects. Addressing these challenges through comprehensive support services, including genetic counseling, psychological support, and patient education, is essential for improving the quality of life and overall well-being of these patients.

SURVEILLANCE AND MANAGEMENT STRATEGIES IN BRCA-MUTATED TRIPLE-NEGATIVE BREAST CANCER

Tailoring Approaches for Optimal Patient Outcomes

Effective surveillance and management strategies are crucial in BRCA-mutated triple-negative breast cancer (TNBC) to ensure timely detection and intervention, ultimately improving patient outcomes. This approach requires a comprehensive understanding of the unique challenges posed by this subtype of breast cancer.

Surveillance Protocols

Regular surveillance is key in managing patients with BRCA-mutated TNBC. Ye et al. (2020) provided insights into the impacts of BRCA mutations on the clinicopathology and management of early-onset TNBC, emphasizing the need for tailored surveillance protocols. These protocols may include more frequent imaging and clinical examinations to monitor for recurrence or new primary cancers.

Risk Reduction Strategies

Risk reduction strategies, including prophylactic surgeries and lifestyle modifications, are important considerations in BRCA-mutated TNBC. Franceschini et al. (2019) discussed bilateral prophylactic mastectomy in BRCA mutation carriers, highlighting the role of such interventions in reducing cancer risk. Additionally, Ghimire et al. (2023) explored cancer risk and characteristics in older female BRCA1/2 mutation carriers, providing valuable information for risk assessment and management.

Management of Early Stage TNBC

The management of early-stage TNBC in BRCA mutation carriers requires a multidisciplinary approach. Mittendorf (2022) discussed optimizing the management of early-stage TNBC, underscoring the importance of individualized treatment plans that consider the patient’s genetic profile.

Genetic Testing and Counseling

Genetic testing and counseling are integral components of managing BRCA-mutated TNBC. Margossian et al. (2020) analyzed BRCA1/2 tests and variants of uncertain significance across a breast center population, demonstrating the complexity of genetic testing and the need for expert interpretation and counseling.

High-Risk Screening

High-risk screening protocols are essential for BRCA mutation carriers. Kataoka (2021) emphasized the importance of up-to-date high-risk screening in hereditary breast and ovarian cancer (HBOC) syndromes, including TNBC with BRCA mutations. These screening protocols may involve advanced imaging techniques and more frequent screenings compared to the general population.

In conclusion, the surveillance and management of BRCA-mutated TNBC require a comprehensive and personalized approach. Tailored surveillance protocols, risk reduction strategies, individualized treatment plans, genetic testing and counseling, and high-risk screening are key components of effective management. Ongoing research and clinical advancements are essential to refine these strategies and improve outcomes for patients with this challenging subtype of breast cancer.

DISCUSSION

Integrating Comprehensive Care in BRCA-Mutated Triple-Negative Breast Cancer

The management of BRCA-mutated triple-negative breast cancer (TNBC) presents unique challenges due to its aggressive nature, complex genetic underpinnings, and significant psychosocial impact. This discussion synthesizes the key aspects of managing this subtype of breast cancer, emphasizing the need for a multidisciplinary and patient-centered approach.

Genetic Counseling and Psychosocial Support

The role of genetic counseling in BRCA-mutated TNBC is pivotal, not only for guiding treatment decisions but also for addressing the psychosocial impact of the diagnosis. As highlighted by Kihn-Alarcón et al. (2023), genetic testing for BRCA mutations necessitates comprehensive counseling to help patients and their families understand the implications of the test results. The emotional and psychological burden associated with this diagnosis, as discussed by Paris et al. (2020) and Kim et al. (2022), underscores the need for robust psychosocial support systems.

Surveillance and Risk Reduction

Effective surveillance and risk reduction strategies are critical in managing BRCA-mutated TNBC. Regular monitoring, as suggested by Ye et al. (2020), and consideration of prophylactic measures, such as bilateral prophylactic mastectomy (Franceschini et al., 2019), are essential components of patient care. Additionally, Ghimire et al. (2023) emphasized the importance of understanding cancer risk in different age groups and populations, which can inform surveillance protocols and management strategies.

Treatment Approaches and Challenges

The treatment of BRCA-mutated TNBC involves a combination of targeted therapies, chemotherapy, and immunotherapy. The use of PARP inhibitors, as explored by Cortesi et al. (2021), represents a significant advancement in targeting the DNA repair deficiencies inherent in BRCA-mutated cells. However, challenges such as drug resistance, as discussed by Mittendorf (2022) and Margossian et al. (2020), necessitate ongoing research and development of novel therapeutic strategies.

High-Risk Screening and Management

For BRCA mutation carriers, high-risk screening protocols are crucial for early detection and intervention. Kataoka (2021) highlighted the importance of up-to-date screening in managing hereditary breast and ovarian cancer syndromes. Tailoring these screening protocols to individual risk profiles is essential for effective management.

In conclusion, the management of BRCA-mutated TNBC requires a comprehensive approach that encompasses genetic counseling, psychosocial support, tailored surveillance and risk reduction strategies, and personalized treatment plans. Addressing the unique challenges of this breast cancer subtype necessitates a multidisciplinary team effort and ongoing research to improve patient outcomes and quality of life.

CONCLUSION

The comprehensive review of BRCA-mutated triple-negative breast cancer (TNBC) underscores the complexity and challenges inherent in managing this aggressive breast cancer subtype. The integration of genetic counseling, personalized treatment strategies, psychosocial support, and vigilant surveillance protocols forms the cornerstone of effective management for patients with BRCA-mutated TNBC.

Genetic counseling plays a pivotal role in guiding patients and their families through the implications of BRCA mutations, aiding in informed decision-making and risk assessment. The emotional and psychological impact of such a diagnosis necessitates robust psychosocial support systems to address the myriad challenges faced by patients.

In terms of treatment, the advent of targeted therapies, particularly PARP inhibitors, has opened new avenues for managing BRCA-mutated TNBC. However, the challenges of drug resistance and the need for individualized treatment plans highlight the importance of ongoing research and clinical trials.

Surveillance and risk reduction strategies, including regular monitoring and consideration of prophylactic measures, are essential in managing the increased risk associated with BRCA mutations. Tailoring these strategies to individual patient profiles is crucial for early detection and intervention.

The management of BRCA-mutated TNBC requires a multidisciplinary approach, encompassing oncologists, genetic counselors, psychologists, and other healthcare professionals. This collaborative effort is vital for providing comprehensive care that addresses the medical, emotional, and social needs of patients.

In conclusion, BRCA-mutated TNBC presents unique challenges that demand a multifaceted and patient-centered approach. Advancements in genetic testing, targeted therapies, and supportive care continue to improve the prognosis and quality of life for patients with this challenging subtype of breast cancer. Ongoing research and innovation are essential for further advancements in the management of BRCA-mutated TNBC.

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26. Paris, I., Rizza, R., Paolillo, C., Carbognin, L., Calegari, A., Scambia, G., Bria, E., Capoluongo, E., Masetti, R., Urbani, A., Pasqualoni, M., & Santonocito, C. (2020, February 15). Abstract P3-05-06: Impact on outcome and response to neoadiuvant chemotherapy in triple negative breast cancer patients and BRCA mutations. Poster Session Abstracts. Abstracts: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, Texas. https://doi.org/10.1158/1538-7445.sabcs19-p3-05-06
27. Kim, S. W., Kim, T. H., Han, J. Y., Kim, S. K., Lee, J. R., Jee, U. C., Suh, C. S., & Kim, S. H. (2022). Impact of BRCA mutations and hormone receptor status on reproductive potential in breast cancer patients undergoing fertility preservation. Gynecological Endocrinology: The Official Journal of the International Society of Gynecological Endocrinology, 38(3), 227–230. https://doi.org/10.1080/09513590.2021.2002294
28. Pogoda, K., Niwińska, A., Sarnowska, E., Nowakowska, D., Jagiełło-Gruszfeld, A., Siedlecki, J., & Nowecki, Z. (2020). Effects of BRCA germline mutations on triple-negative breast cancer prognosis. Journal of Oncology, 2020, 8545643. https://doi.org/10.1155/2020/8545643
29. Lin, P.-H., Chen, S.-C., Tseng, L.-M., Chang, K.-J., Huang, A.-C., Cheng, K.-C., Yang, K., Wu, H.-C., Chao, T.-Y., Chang, Y.-C., Lin, P.-C., Kuo, W.-H., Kuo, W.-L., Lin, C.-H., Chen, H.-M., Yeh, D.-C., Liu, L.-C., Liu, C.-Y., Wang, M.-Y., … Huang, C.-S. (2022). Impact of BRCA mutation on the survival and risk of contralateral breast cancer in Asian breast cancer patients. Breast Cancer Research and Treatment, 192(3), 629–637. https://doi.org/10.1007/s10549-021-06446-7
30. Ye, F., He, M., Huang, L., Lang, G., Hu, X., Shao, Z., Di, G., & Cao, A. (2020). Insights into the impacts of BRCA mutations on clinicopathology and management of early-onset triple-negative breast cancer. Frontiers in Oncology, 10, 574813. https://doi.org/10.3389/fonc.2020.574813
31. Franceschini, G., Di Leone, A., Terribile, D., Sanchez, M. A., & Masetti, R. (2019). Bilateral prophylactic mastectomy in BRCA mutation carriers: what surgeons need to know. Annali Italiani Di Chirurgia, 90, 1–2. https://www.ncbi.nlm.nih.gov/pubmed/30872561
32. Ghimire, B., Karki, U., Shrotriya, S., Rangarajan, T., & Zakalik, D. (2023). Cancer risk and characteristics in older female BRCA1/2 mutation carriers. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 41(16_suppl), 10610–10610. https://doi.org/10.1200/jco.2023.41.16_suppl.10610
33. Mittendorf, E. (2022). Abstract ES5-2: Optimizing the management of early stage TNBC. Cancer Research, 82(4_Supplement), ES5-2-ES5-2. https://doi.org/10.1158/1538-7445.sabcs21-es5-2
34. Margossian, A. L., Nicastro, A. I., & Colica, M. V. (2020, February 15). Abstract P6-08-30:BRCA1/2 tests and beyond, across a breast center population: 10 years analysis and review of mutations and variants of uncertain significance. Poster Session Abstracts. Abstracts: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, Texas. https://doi.org/10.1158/1538-7445.sabcs19-p6-08-30
35. Kataoka, M. (2021). Editorial: HBOC and high-risk screening: up-to-date. Breast Cancer (Tokyo, Japan), 28(6), 1165–1166. https://doi.org/10.1007/s12282-021-01284-3
36. Kihn-Alarcón, A., Marroquin Flores, D. B., de Falla, V., Siliézar, M., Silva, C., & Velarde, A. (2023). BRCA mutations in triple negative breast cancer patients in Guatemala: A descriptive study. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 41(16_suppl), e22543–e22543. https://doi.org/10.1200/jco.2023.41.16_suppl.e22543
37. Paris, I., Rizza, R., Paolillo, C., Carbognin, L., Calegari, A., Scambia, G., Bria, E., Capoluongo, E., Masetti, R., Urbani, A., Pasqualoni, M., & Santonocito, C. (2020, February 15). Abstract P3-05-06: Impact on outcome and response to neoadiuvant chemotherapy in triple negative breast cancer patients and BRCA mutations. Poster Session Abstracts. Abstracts: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, Texas. https://doi.org/10.1158/1538-7445.sabcs19-p3-05-06
38. Kim, S. W., Kim, T. H., Han, J. Y., Kim, S. K., Lee, J. R., Jee, U. C., Suh, C. S., & Kim, S. H. (2022). Impact of BRCA mutations and hormone receptor status on reproductive potential in breast cancer patients undergoing fertility preservation. Gynecological Endocrinology: The Official Journal of the International Society of Gynecological Endocrinology, 38(3), 227–230. https://doi.org/10.1080/09513590.2021.2002294
39. Franceschini, G., Di Leone, A., Terribile, D., Sanchez, M. A., & Masetti, R. (2019). Bilateral prophylactic mastectomy in BRCA mutation carriers: what surgeons need to know. Annali Italiani Di Chirurgia, 90, 1–2. https://www.ncbi.nlm.nih.gov/pubmed/30872561
40. Ghimire, B., Karki, U., Shrotriya, S., Rangarajan, T., & Zakalik, D. (2023). Cancer risk and characteristics in older female BRCA1/2 mutation carriers. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 41(16_suppl), 10610–10610. https://doi.org/10.1200/jco.2023.41.16_suppl.10610
41. Cortesi, L., Rugo, H. S., & Jackisch, C. (2021). An overview of PARP inhibitors for the treatment of breast cancer. Targeted Oncology, 16(3), 255–282. https://doi.org/10.1007/s11523-021-00796-4
42. Mittendorf, E. (2022). Abstract ES5-2: Optimizing the management of early stage TNBC. Cancer Research, 82(4_Supplement), ES5-2-ES5-2. https://doi.org/10.1158/1538-7445.sabcs21-es5-2
43. Margossian, A. L., Nicastro, A. I., & Colica, M. V. (2020, February 15). Abstract P6-08-30:BRCA1/2 tests and beyond, across a breast center population: 10 years analysis and review of mutations and variants of uncertain significance. Poster Session Abstracts. Abstracts: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, Texas. https://doi.org/10.1158/1538-7445.sabcs19-p6-08-30
44. Kataoka, M. (2021). Editorial: HBOC and high-risk screening: up-to-date. Breast Cancer (Tokyo, Japan), 28(6), 1165–1166. https://doi.org/10.1007/s12282-021-01284-3