Drug-induced liver injury and acute pancreatitis during trastuzumab therapy in a BRCA1-mutated, HER2-positive breast cancer patient: a case report

Background

Breast cancer is the most common cancer diagnosed in women and the second leading cause of cancer-related death worldwide (4). According to data from 2020, more than 2.3 million new cases and 685,000 deaths were recorded, which underscores the urgent need to improve its diagnosis, treatment, and prevention (5). Major risk factors include gender, age, race, BRCA1 and BRCA2 mutations, early menarche, late menopause, dense breast tissue, long-term hormone replacement therapy, hormonal contraception, history of removal of benign breast lesions containing atypical ductal or lobular hyperplasia (ADH, ALH), overweight and obesity (4). Mammography is the only population-based method with proven effectiveness for early detection and has the greatest impact on reducing mortality in women aged 50–70 years (2).

Chemotherapy and targeted anti-human epidermal growth factor receptor 2 (HER2) therapy, including the monoclonal antibody trastuzumab, are the standard of care for HER2-positive breast cancer, and have significantly improved patient prognosis (6). Although this treatment is generally well tolerated, it carries a risk of adverse effects, the most commonly reported of which is cardiotoxicity, which can lead to the development of heart failure (7). Less common but potentially serious complications, which may complicate the course of treatment due to their severity, include drug-induced autoimmune disorders such as hepatitis and pancreatitis (8,9). Genetic testing for BRCA1 and BRCA2 mutations can guide optimal therapeutic and preventive strategies in breast cancer patients (6).

Clostridioides difficile infection (CDI) is an important complication in cancer patients, particularly during chemotherapy or antibiotic therapy. CDI can cause severe diarrhea and may require delays or modifications in cancer treatment, negatively affecting prognosis (10,11).

Introduction

Breast cancer is a heterogeneous group of diseases, comprising multiple subtypes with distinct biological features that influence response to various treatment modalities and clinical outcomes (12). Germline mutations in BRCA1 and BRCA2 are major hereditary risk factors for breast and ovarian cancers in women and are predominantly associated with triple-negative breast cancers (TNBC) (13). ERBB2 gene amplification, resulting in overexpression of the HER2 receptor, occurs in approximately 20% of breast cancer patients and is an important prognostic and predictive factor (3). In HER2-positive patients, breast cancer grows faster, has a more aggressive course, and is more drug-resistant (14). True HER2-amplified breast cancers are rare among BRCA1 mutation carriers, with reported prevalence ranging from 2.1% to 2.5%, and slightly higher in BRCA2 mutation carriers (up to 6.8%) (15). HER2-positive tumors are significantly more frequent in BRCA2 than BRCA1 carriers (21.7% vs. 5.8%) (16). The coexistence of HER2 overexpression and BRCA mutations is biologically unusual, complicating decisions regarding targeted therapy and clinical management (1).

Here, we report a case of a 41-year-old woman with BRCA1-mutated, HER2-positive breast cancer who developed rare multi-organ complications during trastuzumab-based therapy, illustrating the therapeutic challenges and clinical relevance of this uncommon phenotype.

Objective

The aim of this case report is to present rare and previously undescribed complications associated with the use of trastuzumab. We present this article in accordance with the CARE reporting checklist (available at https://cco.amegroups.com/article/view/10.21037/cco-2025-aw-148/rc).

Case presentation

In November 2022, a 41-year-old patient underwent a breast ultrasound examination, which revealed a 0.6 cm × 0.3 cm lesion, qualifying her for observation. The clinical course of the patient, including interventions, laboratory values, and complications, is summarized in Table 1. In May 2023, the presence of a focally solid, hypoechoic lesion with irregular contours was confirmed, which had enlarged to 1.5 cm × 1.1 cm × 0.8 cm. After a biopsy, she was diagnosed with invasive not otherwise specified (NOS) G3 breast cancer, characterised by HER2 receptor overexpression in fluorescence in situ hybridization (FISH) assessment, with no expression of ER and PgR hormone receptors and a Ki67 index of 95%. Genetic testing revealed the presence of a BRCA1 mutation. In accordance with the guidelines in force in Poland, between August and November 2023, the patient received five cycles of chemoimmunotherapy—containing carboplatin, paclitaxel and trastuzumab, at doses recommended for this type of breast cancer. They were administered every 21 days. The last infusion before surgery was administered on 30 November 2023, after which the patient was hospitalised due to drug-induced liver injury (DILI). Transaminase values exceeded 5× upper limit of normal (ULN). The patient was admitted to hospital with alanine transaminase (ALT) values of 1,044 IU/L and aspartate transaminase (AST) values of 933 IU/L. During hospitalization, the following laboratory investigations were performed: alpha-fetoprotein (AFP) 3.3 ng/mL (within the reference range), anti-hepatitis A virus (HAV) immunoglobulin G (IgG), anti-hepatitis B core (HBc) immunoglobulin M (IgM), and anti-hepatitis C virus (HCV) antibodies. Active infection with hepatotropic viruses [hepatitis B virus (HBV), HCV, HAV] was excluded. No liver-specific autoantibodies were detected, and serum protein electrophoresis revealed no abnormalities. Further evaluation included anti-mitochondrial antibodies (AMA M2 subtype), antinuclear antibody (ANA) screening, anti-liver kidney microsomal type 1 antibodies (anti-LKM-1), and anti-smooth muscle antibodies (ASMA) assessed by indirect immunofluorescence. In addition, hepatitis B surface antigen (HBsAg), a fourth-generation human immunodeficiency virus (HIV) antigen/antibody combination assay, activated partial thromboplastin time (aPTT), ceruloplasmin, creatine kinase, C-reactive protein (CRP) and thyroid-stimulating hormone (TSH) were measured. Microbiological culture targeting Enterobacteriaceae species was also performed. Given the persistent normalization of aminotransferase activity, liver biopsy was deferred. Due to the onset of toxicity, the patient did not receive the sixth cycle, but in January 2024 she underwent a bilateral mastectomy with nipple transplantation to the groin area (the procedure was performed with a view to future reconstruction), with a microscopic pathologic complete response (pCR) effect—complete remission. After the surgery, in accordance with the guidelines for breast cancer treatment in force in Poland, a decision was made to attempt to reintroduce immunotherapy, which, however, was discontinued after the first cycle due to a renewed increase in transaminase levels, this time to >15× ULN, and the appearance of autoimmune symptoms. During treatment with trastuzumab, the patient experienced complications in the form of drug-induced liver damage, which required hospitalisation. Between 9 and 20 February 2024, the patient was hospitalised again, this time due to acute pancreatitis (AP). On admission, she reported epigastric pain, nausea, and redness and tenderness of the right mastectomy site. Laboratory tests revealed elevated inflammatory and liver parameters: CRP 23.7 mg/L, while transaminase levels did not exceed 5× ULN. The amylase level was also measured at 1,235 U/L, which was nearly ten times the ULN. Serum lipase was not measured. An ultrasound examination performed during the hospital stay on February 12th showed a slight enlargement of the pancreas with preserved normal echostructure, without visible focal lesions. The patient also reported persistent diarrhoea. Microbiological examination of stool samples was positive for Clostridioides difficile. Prior to the onset of diarrhoea, the patient had received intravenous piperacillin/tazobactam followed by oral amoxicillin/clavulanic acid. The temporal relationship between antibiotic exposure and symptom onset suggests antibiotic-associated dysbiosis as the most likely contributing factor, in addition to prior chemotherapy and immunotherapy. Oral vancomycin treatment was initiated. During hospitalisation, improvement in clinical condition, resolution of pain, normalisation of inflammatory parameters and resolution of diarrhoea were observed.

In October 2024, due to drug-induced liver and pancreas damage, a follow-up ultrasound examination was performed. A fragmentarily visible, slightly enlarged liver with increased echogenicity and signs of steatosis, without focal lesions, was found. The examination of the pancreas was difficult due to its poor visibility and the possibility of examining only part of the head and body. In the visible area, it was not enlarged, with homogeneous, increased echogenicity and signs of steatosis. Currently (September 2025), the patient remains without signs of active disease or gastrointestinal symptoms.

The patient presented has a mutation in the BRCA1 gene, and her breast cancer is characterised by positive HER2 gene expression. Her mother, also a carrier of this mutation, was treated for bilateral breast cancer, ovarian cancer and kidney cancer.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Breast cancer in women aged 40 years or younger carrying germline BRCA1/2 mutations is uncommon but often associated with aggressive clinical and pathological features. HER2-positive tumors in this rare patient subset are particularly unusual, highlighting limited data on optimal targeted therapy and prognosis (17). Genetic testing for BRCA1 and BRCA2 mutations informs optimal therapeutic and preventive strategies in breast cancer patients (6).

Recent data indicate that ER-low/HER2-negative tumors exhibit BRCA1/2 mutation rates comparable to TNBC, suggesting that restrictive testing criteria based solely on hormone receptor expression may miss mutation carriers (18). BRCA1 and HER2/neu are located close together on chromosome 17, but studies show that BRCA1-associated tumors rarely exhibit HER2 amplification or overexpression. This suggests that BRCA1-driven cancers and HER2-positive tumors may follow distinct molecular pathways (19). Typically, BRCA1-associated breast cancers are high-grade, poorly differentiated, estrogen- and progesterone-receptor negative, often basal-like, while HER2 overexpression is uncommon in both BRCA1- and BRCA2-related tumors (19,20). When HER2 positivity occurs in BRCA1 carriers, it may involve large BRCA1 rearrangements and a complex treatment course (21).

Although BRCA1 and BRCA2-associated breast cancers are often grouped together, emerging evidence suggests distinct biological behaviors and differential sensitivity to systemic therapies depending on the affected gene. These differences further support the need for individualized therapeutic strategies in BRCA-mutated breast cancer, particularly in rare phenotypes such as HER2-positive tumors in BRCA1 carriers (22).

Experimental data suggest potential interactions between BRCA1/2 mutations and HER2 amplification through pathways such as iNOS/NO, which may contribute to tumor aggressiveness, though clinical significance remains unclear (23).

In a cohort of 398 BRCA-mutated patients, HER2 positivity was observed in 5.4% of BRCA1 and 9.5% of BRCA2 carriers, with a pooled prevalence of 9.1% across more than 21,000 patients. These findings confirm that although uncommon, the coexistence of BRCA mutations and HER2 overexpression represents a clinically relevant subgroup (24). True HER2 amplification is rare, occurring in 2–7% of BRCA1/2-associated breast cancers (15), and nearly 25% of bilateral tumors show discordance in HER2 status (24).

HER2-positive breast cancer in germline BRCA1/2 mutation carriers is rare but clinically significant, with high histologic grade, high proliferation rates, and predominance of BRCA2 mutations. This co-occurrence is associated with worse overall survival compared with either HER2-positive/BRCA wild-type or HER2-negative/BRCA-mutated tumors, supporting exploration of combined therapeutic strategies, such as PARP inhibitors plus anti-HER2 agents, in dedicated trials (19).

A retrospective cohort of 700 BRCA-tested patients confirmed that HER2-positive tumors in BRCA1 carriers show higher histological malignancy and proliferation, co-occurrence of BRCA mutations and HER2 overexpression is associated with a significantly worse prognosis—the hazard ratio (HR) for overall survival was 3.4 [95% confidence interval (CI): 1.3–16.7] (1).

Our case aligns with these findings and highlights the need to better characterize HER2-positive disease in BRCA1 carriers.

HER2-positive cancer accounts for approximately 20% of all breast cancer cases and is associated with a more aggressive clinical course and poorer prognosis compared to other biological subtypes (6). HER2 is a transmembrane tyrosine receptor encoded by the ERBB2 gene located on the long arm of chromosome 17, playing a key role in cell proliferation and apoptosis; its amplification leads to HER2 protein overexpression in cancer cells (14).

Trastuzumab is a recombinant, humanised monoclonal antibody directed against the IgG1 class HER2 protein. It binds to the extracellular domain of the HER2 protein, inhibiting excessive tumour proliferation, which results in the arrest of the cell cycle in the G1 phase (14). According to the Summary of Product Characteristics (SmPC), trastuzumab (Herceptin) should only be used in patients with HER2 receptor overexpression or HER2 gene amplification, i.e. in HER2-positive patients (25). In our patient, trastuzumab-based therapy resulted in a complete pathological response, which is associated with improved progression-free and overall survival (6).

Although anti-HER2 therapies remain the standard of care, patients with HER2-positive disease have historically been excluded from clinical trials evaluating PARP inhibitors, which have demonstrated efficacy in BRCA-mutated, HER2-negative breast cancer (19,24). Emerging evidence suggests that this subgroup should not be excluded a priori from targeted therapeutic strategies (24).

Adjuvant olaparib significantly improves invasive and distant disease-free survival in patients with high-risk, HER2-negative early breast cancer and germline BRCA1/2 mutations (26), as demonstrated in landmark trials such as OlympiAD and EMBRACA, which exploit synthetic lethality in homologous recombination-deficient tumors (27). However, the role of PARP inhibitors in HER2-positive disease remains unclear.

According to the guidelines of the European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO), PARP inhibitors are recommended for patients with BRCA1/2 mutations and early or advanced breast cancer, but usually in the context of HER2-negative tumours. The latest ESMO recommendations [2023] emphasise that data on the efficacy of PARP inhibitors in the HER2-positive population are limited and require further clinical research. ASCO also does not recommend the routine use of PARP inhibitors in HER2+ patients with BRCA mutations due to insufficient data (28,29).

According to the Drug Programme in force in Poland, PARP inhibitors (in this case Olaparib) can only be used in patients with HER2-negative breast cancer and a confirmed BRCA1/2 mutation. This means that patients with the BRCA1+/HER2+ phenotype—such as the patient described—are not eligible for treatment with this drug under the public health insurance scheme, despite the potential benefits of targeted therapy in this high-risk group. In light of the available clinical data, it seems reasonable to further evaluate the efficacy of combined therapeutic strategies in the group of patients with double molecular aberration BRCA+/HER2+ and to possibly revise the reimbursement criteria in Drug Programmes (30).

These limitations highlight an important therapeutic gap and underscore the need for dedicated clinical trials and more personalized treatment strategies for this rare, high-risk subgroup of patients.

While targeted therapy provides significant clinical benefit in this setting, it may also be associated with rare and potentially severe adverse events. The patient developed multiple serious complications, including DILI, AP, and CDI. While cardiotoxicity is the best-known adverse effect of trastuzumab, there are increasing reports of hepatotoxicity and pancreatitis, particularly when combined with chemotherapy (8,9). The mechanism by which trastuzumab alone may lead to liver injury or pancreatitis remains unclear; however, the clinical presentation in this case suggests an idiosyncratic rather than dose-dependent reaction, underscoring the importance of close biochemical monitoring during treatment.

The De Ritis ratio (AST/ALT), which was <1 in this patient, supports a non-alcoholic, potentially drug-related etiology of liver injury. Ratios <1 are typically associated with viral, metabolic, or drug-induced causes, whereas values >1 are more often seen in alcohol-related liver disease (31).

To assess the probability of adverse drug reactions (ADRs), the Naranjo scale is used, developed in 1991 by Naranjo and colleagues at the University of Toronto. It consists of 10 questions that help determine whether a causal relationship exists between the administered drug and the adverse effects that occurred. The questions require “yes”, “no”, or “do not know” responses. Points are assigned for each answer, yielding a total score ranging from −4 to +13 (32). The described patient scored 8/9 points, which indicates that it is highly probable that the reported adverse effects were caused by trastuzumab. The one-point variation results from an equivocal answer to the question regarding previous conclusive reports of this reaction. Although similar toxicities have been more commonly described with antibody-drug conjugates such as trastuzumab emtansine, reports associated with trastuzumab monotherapy remain limited.

The occurrence of DILI is favoured by, among other things, female gender, genetic factors and the simultaneous use of multiple medications (polypharmacy) (35). The patient described met at least two of these criteria – she was female and was taking numerous medications, including chemotherapeutics and antibiotics.

DILI can arise as a result of two basic mechanisms. The first is the direct, predictable hepatotoxicity of a given drug. In the case of trastuzumab, according to the Summary of Product Characteristics (SmPC), the most common adverse reactions include allergic reactions, cardiotoxicity and respiratory disorders, while hepatotoxicity is not described (25). Therefore, the second mechanism seems more likely—an idiosyncratic reaction, i.e. an unpredictable, excessive reaction of the body, independent of the dose of the drug (35). It can occur after almost any drug, and symptoms may appear even several months after exposure. To determine whether the administered drug could have caused DILI, the Roussel Uclaf Causality Assessment Method (RUCAM) is used. Since there is no specific biochemical test that unequivocally confirms DILI, the diagnosis is based on excluding other causes, such as viral or autoimmune hepatitis (36). One of the RUCAM criteria is the sudden onset of symptoms within a few days after drug administration and improvement in clinical status after its discontinuation. In the described patient, both of these criteria were met, and other previously mentioned causes of DILI were additionally excluded.

AP is also a condition that has probably occurred after the use of trastuzumab. AP is an acute inflammatory process of the gland, involving adjacent tissues. It is a serious disease resulting from self-digestion of the organ due to the release and activation of trypsinogen and other enzymes (37). The medical literature to date (as of July 2025) does not describe cases of AP typically following the use of trastuzumab, but a case has been described following the use of trastuzumab emtansine, which is an antibody-drug conjugate (38). The exact mechanism is not fully understood, but it is believed to be a rare idiosyncratic reaction of the body, involving direct toxicity or an immune response in the pancreas (9).

CDI is one of the most common complications in cancer patients undergoing chemotherapy, especially with prior antibiotic use and immunosuppression, leading to gut microbiota disturbances and excessive C. difficile proliferation (10,11).

Breast cancer patients are particularly vulnerable to developing this infection, which can manifest as severe diarrhoea and lead to delays or the need to change cancer treatment, which in turn negatively affects prognosis (11).

Diarrhoea can be caused by both chemotherapy and the cancer itself. Diarrhoea can lead to secondary complications such as dehydration, water and electrolyte imbalances, and acid-base imbalances. It also leads to bacterial and fungal infections, malnutrition and wasting. These symptoms may force the discontinuation of treatment or the use of suboptimal treatment, thereby reducing the effectiveness of treatment (33).

In this case, treatment with vancomycin resulted in rapid clinical improvement, but the combined presence of three serious complications—hepatotoxicity, pancreatitis and CDI—forced the discontinuation of immunotherapy, illustrating how multidimensional and difficult the treatment of malignant tumours can be. It also points to the need for close clinical monitoring, early diagnosis of adverse effects and individualisation of therapy.

This case report has some limitations. It describes only a single patient, so the findings cannot be generalized. AP was diagnosed clinically and with elevated amylase and ultrasound, but lipase levels were not available, limiting confirmation of organ injury. Liver biopsy was also not performed due to normalization of aminotransferase levels during hospitalization, precluding histopathological verification of liver injury. Although extensive laboratory testing was performed to exclude viral and autoimmune causes, the exact mechanism linking trastuzumab to the observed complications cannot be definitively established. Some patient background, such as psychosocial history, was also not available. Despite these limitations, this case highlights rare but clinically significant complications associated with trastuzumab therapy in a BRCA1-mutated, HER2-positive patient. It emphasizes the need for careful monitoring and suggests that idiosyncratic toxicity may occur even in the absence of combination therapy, warranting further investigation in this unique patient population.

Conclusions

This case highlights the rare coexistence of HER2-positive breast cancer in a BRCA1 mutation carrier, supporting the hypothesis that such tumors may represent phenocopies and require individualized therapeutic approaches.

Importantly, it demonstrates the occurrence of multiple uncommon but clinically significant adverse events during trastuzumab therapy, including DILI and AP, most likely of an idiosyncratic nature. Gastrointestinal complications are common during cancer treatment, especially when chemotherapy is used (34). These complications led to treatment interruption despite an excellent oncological response.

This case underscores the importance of individualized cancer treatment and vigilant monitoring for rare adverse events, which can significantly impact therapy and patient quality of life. It also contributes to the discussion on the potential expansion of PARP inhibitor reimbursement for patients with HER2-positive and BRCA1-mutated breast cancer.

Complications from the gastrointestinal tract, including vomiting, diarrhea, inflammation of the mucous membranes of the mouth, stomach, and intestines, as well as neutropenic enterocolitis, are common consequences of oncological treatment, especially when chemotherapy is used. Although the occurrence of AP and DILI following trastuzumab therapy is not widely described in the literature, it is assumed that this drug may have triggered an idiosyncratic reaction, leading to the development of these two disease entities. To objectively assess the occurrence of adverse effects, the RUCAM and Naranjo scales should be applied.

It is also worth noting that breast cancer is the most common malignant tumor in women, therefore public awareness of its treatment methods and their possible consequences is essential.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://cco.amegroups.com/article/view/10.21037/cco-2025-aw-148/rc

Peer Review File: Available at https://cco.amegroups.com/article/view/10.21037/cco-2025-aw-148/prf

Funding: This work was supported by Faculty of Medical and Health Sciences, Kazimierz Pulaski University of Radom, Poland.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cco.amegroups.com/article/view/10.21037/cco-2025-aw-148/coif). All authors report receiving support from the Kazimierz Pulaski University of Radom. K.K.K. and N.G. report consulting fees from AMCA. R.W. reports coverage of conference attendance costs from Eli Lilly and Novartis. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Viansone A, Pellegrino B, Omarini C, et al. Prognostic significance of germline BRCA mutations in patients with HER2-POSITIVE breast cancer. Breast 2022;65:145-50. [Crossref] [PubMed]
2. Jassem J, Krzakowski M, Bobek-Billewicz B, et al. Breast cancer. Onkol Prakt Klin Edu 2020;6:297-352.
3. Available online: https://onkologia.org.pl/ [accessed on 09.07.2025].
4. Menon G, Alkabban FM, Ferguson T. Breast Cancer. [Updated 2024 Feb 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan. Available online: https://www.ncbi.nlm.nih.gov/books/NBK482286/
5. Stabla V, Zdrodowska M. Analysis of factors influencing breast cancer recurrence. Akademia Zarządzania 2025;9: [Crossref]
6. Chruściana-Bołtuć A, Dubiański R, Tyszka-Kordylas A. Trastuzumab deruxtecan — a new standard of care for advanced breast cancer. Onkol Prakt Klin Edu 2025;11:33-9.
7. Lin A, Rugo HS. The role of trastuzumab in early stage breast cancer: current data and treatment recommendations. Curr Treat Options Oncol 2007;8:47-60. [Crossref] [PubMed]
8. Vucicevic D, Carey EJ, Karlin NJ. Trastuzumab-induced hepatotoxicity: a case report. Breast Care (Basel) 2013;8:146-8. [Crossref] [PubMed]
9. Muzaffar M, Jia J, Liles D, et al. Acute Pancreatitis Associated With Ado-Trastuzumab Emtansine. Am J Ther 2016;23:e572-4. [Crossref] [PubMed]
10. Rodríguez Garzotto A, Mérida García A, Muñoz Unceta N, et al. Risk factors associated with Clostridium difficile infection in adult oncology patients. Support Care Cancer 2015;23:1569-77. [Crossref] [PubMed]
11. Peretz A, Shlomo IB, Nitzan O, et al. Clostridium difficile Infection: Associations with Chemotherapy, Radiation Therapy, and Targeting Therapy Treatments. Curr Med Chem 2016;23:4442-9. [Crossref] [PubMed]
12. Yersal O, Barutca S. Biological subtypes of breast cancer: Prognostic and therapeutic implications. World J Clin Oncol 2014;5:412-24. [Crossref] [PubMed]
13. Oubaddou Y, Ben Ali F, Oubaqui FE, et al. The Tumor Suppressor BRCA1/2, Cancer Susceptibility and Genome Instability in Gynecological and Mammary Cancers. Asian Pac J Cancer Prev 2023;24:3139-53. [Crossref] [PubMed]
14. Marcinkowska M, Stańczyk M, Klajnert-Maculewicz B. Trastuzumab - a monoclonal antibody - and dendrimers in a targeted therapy for breast cancer. Postepy Hig Med Dosw (Online) 2015;69:1313-24. [Crossref] [PubMed]
15. Evans DG, Lalloo F, Howell S, et al. Low prevalence of HER2 positivity amongst BRCA1 and BRCA2 mutation carriers and in primary BRCA screens. Breast Cancer Res Treat 2016;155:597-601. [Crossref] [PubMed]
16. Fountzilas E, Konstantopoulou I, Vagena A, et al. Pathology of BRCA1- and BRCA2-associated Breast Cancers: Known and Less Known Connections. Clin Breast Cancer 2020;20:152-9. [Crossref] [PubMed]
17. Schettini F, Blondeaux E, Molinelli C, et al. Characterization of HER2-low breast cancer in young women with germline BRCA1/2 pathogenetic variants: Results of a large international retrospective cohort study. Cancer 2024;130:2746-62. [Crossref] [PubMed]
18. Yoo JW, Byeon J, Park WK, et al. Germline BRCA1/2 Mutation Prevalence in Unselected ER-Low/HER2-Negative Breast Cancer. Ann Surg Oncol 2026;33:2230-8. [Crossref] [PubMed]
19. Grushko TA, Blackwood MA, Schumm PL, et al. Molecular-cytogenetic analysis of HER-2/neu gene in BRCA1-associated breast cancers. Cancer Res 2002;62:1481-8.
20. Honrado E, Benítez J, Palacios J. Histopathology of BRCA1- and BRCA2-associated breast cancer. Crit Rev Oncol Hematol 2006;59:27-39. [Crossref] [PubMed]
21. Uchida N, Takeshita M, Suda T, et al. HER2-positive breast cancer in a germline BRCA1 gene large deletion carrier. Int Cancer Conf J 2021;10:181-5. [Crossref] [PubMed]
22. Zattarin E, Taglialatela I, Lobefaro R, et al. Breast cancers arising in subjects with germline BRCA1 or BRCA2 mutations: Different biological and clinical entities with potentially diverse therapeutic opportunities. Crit Rev Oncol Hematol 2023;190:104109. [Crossref] [PubMed]
23. Lin K, Baritaki S, Vivarelli S, et al. The Breast Cancer Protooncogenes HER2, BRCA1 and BRCA2 and Their Regulation by the iNOS/NOS2 Axis. Antioxidants (Basel) 2022;11:1195. [Crossref] [PubMed]
24. Tomasello G, Gambini D, Petrelli F, et al. Characterization of the HER2 status in BRCA-mutated breast cancer: a single institutional series and systematic review with pooled analysis. ESMO Open 2022;7:100531. [Crossref] [PubMed]
25. Available online: https://ec.europa.eu/ [accessed on 14 July 2025].
26. Tutt ANJ, Garber JE, Kaufman B, et al. Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. N Engl J Med 2021;384:2394-405. [Crossref] [PubMed]
27. Zhou T, Zhang J. Therapeutic advances and application of PARP inhibitors in breast cancer. Transl Oncol 2025;57:102410. [Crossref] [PubMed]
28. Olaparib. Available online: https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-for-solid-tumours/esmo-mcbs-scorecards?scorecard=331 [accessed on 20 August 2025].
29. Available online: https://www.asco.org/abstracts-presentations/ABSTRACT186720 [accessed on 20 August 2025].
30. Załącznik B.50. Available online: https://www.gov.pl/attachment/45867483-e959-4faa-9a7a-e92def936fb5 [accessed on 20 August 2025].
31. Palka M. Liver and bile duct diseases in General Practice. Lekarz POZ 2017;3:13-6.
32. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Adverse Drug Reaction Probability Scale (Naranjo) in Drug Induced Liver Injury. [Updated 2019 May 4]. Available online: https://www.ncbi.nlm.nih.gov/books/NBK548069/
33. Łacko A. Gastrointestinal and hepatic complications associated with lapatinib treatment. Onkol Prak Klin 2012;8:113-8.
34. Nasiłowska-Adamska B. Prevention and treatment of gastrointestinal disorders accompanying chemotherapy and radiotherapy. Hematologia 2011;2:149-61.
35. Małysz M, Więcek A, Piechaczek M, et al. Drug-induced liver injury (DILI) – mechanisms and diagnosis. Farm Pol 2022;78:460-8.
36. Woroń J, Wordliczek J, Malec-Milewska M. Is the hepatotoxicity of metamizole significant in clinical practice? Ból 2020;21:24-7.
37. Cichońska M, Tokarska L. The role of nurses in identifying risk factors and prevention among people hospitalised with acute pancreatitis. Acta Sci Acad Ostrov:147-98.
38. Early Breast Cancer Trialists’ Collaborative group (EBCTCG). Trastuzumab for early-stage, HER2-positive breast cancer: a meta-analysis of 13 864 women in seven randomised trials. Lancet Oncol 2021;22:1139-50. [Crossref] [PubMed]