Young-onset breast cancer (YOBC) with germline BRCA pathogenic variants (PVs) is associated with an increased risk for all-cause mortality if diagnosed within 10 years after childbirth, according to a study published online April 19 in JAMA Network Open.

Zhenzhen Zhang, Ph.D., M.P.H., from the Oregon Health & Science University in Portland, and colleagues examined whether time between most recent childbirth and BC diagnosis is associated with mortality among patients with YOBC and germline BRCA1/2 PVs in a prospective cohort study. Data were included for 903 women with BRCA PVs diagnosed with stage I to III BC at age 45 years or younger.

Of the participants, 419 received a BC diagnosis zero to less than 10 years after childbirth, including 228 and 191 who were diagnosed less than five years after childbirth and five to less than 10 years after childbirth, respectively. Compared with nulliparous women and women diagnosed 10 or more years after childbirth, women diagnosed within five to less than 10 years after childbirth had increased all-cause mortality (hazard ratio, 1.56). Compared with the nulliparous group, the risk for mortality was greater for women with estrogen-receptor (ER)-positive BC in the group that was less than five years postpartum and for women with ER-negative BC in the group that was five to less than 10 years postpartum (hazard ratios, 2.35 and 3.12, respectively).

“Consideration of the potential impact of childbirth on BC outcomes in young germline BRCA PV carriers may improve standard of care within the realms of genetic counseling, disease prevention, and the clinic,” the authors write.

One author disclosed financial ties to AstraZeneca and Everything Genetic.

Abstract/Full Text

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with challenging management and a poor prognosis. The growth and metastasis of this cancer subtype are associated with the secretion of chemokines and growth factors by tumor-associated macrophages (TAMs). 

Salvianolic acid A (SAA) has anti-cancer properties; however, its role in influencing TAMs in the tumor microenvironment is uncertain. This study used the human TNBC line SUM159, mouse mammary gland tumor cells, and mouse macrophage cells to investigate the role of SAA in influencing TAMs in the tumor microenvironment. The findings are published in the journal Molecules.

Tumor Microenvironment and Polarization of Macrophages

To induce the polarization of TAMs and mediate the development of the tumor microenvironment, TNBC cells were exposed to a conditioned medium (TCM-SUM159 and TCM-4T1). This medium facilitated the polarization of macrophages into M2-like TAMs.

Co-Cultured Macrophages and Expression of Growth Factors

The infiltration of M2 TAMs in cancer cells is significantly correlated with the expression of transforming growth factor beta-1 (TGF-ß1), which in turn further activates M2 TAMs. Additionally, culturing TAMs in a conditioned medium with TNBC cells also activates the extracellular signal-regulated kinase (ERK) signaling pathway.

Co-Cultured Macrophages and Expression of Cytokines

The messenger ribonucleic acid (mRNA) expression of arginase 1 (Arg-1) decreased, whereas mRNA expression of interleukin (IL)-1ß, CD86, and inducible nitric oxide synthase (iNOS) increased in the co-cultured macrophages after treatment with SAA.

Salvianolic Acid A and Inhibition of Macrophage Polarization, Migration, and Invasion

Treatment with SAA inhibited the polarization of cells into M2-like TAMs. SAA also inhibited the migration and invasion of TNBC cells by these macrophages. This was mediated by the repolarization of M2-like TAMs into M1-like TAMs.

Salvianolic Acid A and Macrophage Expression of Growth Factors

Treatment with SAA was found to be associated with a decrease in TGF-ß1 expression levels, whereas the total ERK remained unchanged. The results also indicate an increase in the expression levels of iNOS.

Source:

Tang, C., Jiang, S. Y., Li, C., Jia, X., & Yang, W. (2024). The effect of salvianolic acid A on Tumor-Associated macrophage polarization and its mechanisms in the tumor microenvironment of Triple-Negative breast Cancer. Molecules (Basel. Online), 29(7), 1469. https://doi.org/10.3390/molecules29071469 

Cryoablation can be performed effectively in nonsurgical breast cancer patients with varying tumors, according to a study presented at the annual meeting of the Society of Interventional Radiology, held from March 23 to 28 in Salt Lake City.

Jolie Jean, M.D., from Weill Cornell, and Yolanda Bryce, M.D., from the Memorial Sloan Kettering Cancer Center, both in New York City, presented their technique for cryoablation of primary breast cancer (treated from January 2017 to March 2023). The analysis included 60 patients with breast cancer (48 had invasive ductal carcinoma) who were poor surgical candidates or refused surgery.

The researchers found that during a median follow-up of 16 months, there was a recurrence rate of 10 percent (six patients). The risk for recurrence was higher among patients with poorly differentiated disease (risk ratio, 5.5). Invasive lobular carcinoma, estrogen receptor or progesterone receptor, and triple-negative status were not associated with risk. Furthermore, tumor size was similar between the recurrence and nonrecurrence groups (2.53 and 2.54 cm, respectively).

“Surgery is still the best option for tumor removal, but there are thousands of women who, for various reasons, cannot have surgery,” Bryce said in a statement. “We are optimistic that this can give more women hope on their treatment journeys.”

Press Release

More Information

For over three decades, radiotherapy has been an essential part of the treatment following breast-conserving surgery (BCS) for patients with early-stage breast cancer. Recent studies have shown that there is a low risk of ipsilateral breast events (IBEs) or other recurrences among selected patients aged 65–70 years or older with stage I breast cancers who are treated with BCS and endocrine therapy (ET) without adjuvant radiotherapy. 

This prospective multicenter cohort trial, published in the Journal of Clinical Oncology, assessed whether younger postmenopausal patients could also be effectively managed without radiation therapy by using a genomic assay in addition to traditional selection criteria. Moreover, to investigate the feasibility of omitting radiotherapy in postmenopausal patients who meet specific criteria.

Baseline Characteristics

A total of 200 eligible patients were enrolled in the study. This was a single-arm trial enrolling postmenopausal patients aged 50–69 years with pT1N0 unifocal invasive breast cancer. Eligible patients had margins of ≥2 mm after BCS and tumors that were estrogen receptor-positive, progesterone receptor-positive, and human epidermal growth factor receptor 2-negative, with an Oncotype DX 21-gene recurrence score ≤18. The primary endpoint of the study was the rate of loco-regional recurrence 5 years post-BCS.

The mean age was 62 ± 4.9 years, with a mean 21-gene recurrence score of 11.2 ± 4.8. The tumors were mostly grade 1 or 2, with an average size of 10 mm ± 4.6. Lymphovascular invasion was observed in 16 tumors, and 11 cases had an extensive intraductal component.

Favorable Survival Rates and Low Mortality 

The follow-up duration was 5.21 years (IQR, 5.01–5.97). Out of the 186 patients who had a clinical follow-up of at least 56 months, the overall and breast cancer-specific survival rates at 5 years were both 100%. During the study period, there were two deaths, resulting in a 1% mortality rate. One death occurred in a patient who was lost to clinical follow-up, and the cause of death could not be determined. The other death was attributed to unrelated endometrial carcinosarcoma.

High 5-Year Freedom from Recurrence 

The 5-year freedom from any recurrence was 99% (95% CI, 96–100). Two events occurred within 5 years: one ipsilateral axillary recurrence and one ipsilateral breast event (IBE). Six additional recurrences occurred after 5 years, all IBEs. No distant recurrences were observed during the study period.

Endocrine Therapy Compliance and Recurrence Patterns 

A total of 169 patients remained compliant with ET, and 184 patients were event-free at 5 years. Among the six patients who experienced a recurrence after 5 years, three were compliant with ET. Additionally, 154 out of 178 patients who had not recurred by 5 years were compliant. It is worth noting that both patients who experienced a recurrence before 5 years were compliant with ET. Out of the 14 patients with less than 56 months of clinical follow-up, nine were compliant with ET at the time of data submission.

Age-Based Differences in IBE and Overall Recurrence Rates

The rate of IBEs was 3.6% in the 60–69 year age group and 3.3% in the 50–59 year age group. Similarly, the rate of overall recurrence was 3.6% in the 60–69 year age group and 5.0% in the 50–59 year age group.

Source:

Jagsi, R., Griffith, K. A., Harris, E., Wright, J. L., Recht, A., Taghian, A. G., Lee, L., Moran, M. S., Small, W., Johnstone, C., Rahimi, A., Freedman, G. M., Muzaffar, M., Haffty, B. G., Horst, K. C., Powell, S. N., Sharp, J., Sabel, M. S., Schott, A. F., & El‐Tamer, M. (2023). Omission of Radiotherapy after Breast-Conserving Surgery for women with breast Cancer with low clinical and genomic risk: 5-Year Outcomes of IDEA. Journal of Clinical Oncology, 42(4), 390-398.  https://doi.org/10.1200/jco.23.02270 

High mammographic density is a major risk factor for breast cancer, contributing to approximately 30% of all breast cancer. There is a lack of research regarding the local biological effects of anti-inflammatory drugs in dense breast tissue. 

A randomized, controlled, phase II clinical trial published in the journal Breast Cancer Research examined the effects of low-dose acetylsalicylic acid (ASA) on the inflammatory microenvironment and magnetic resonance imaging (MRI) parameters in dense breast tissue in postmenopausal women.

Participant Characteristics

A total of 53 healthy postmenopausal women with Breast Imaging Reporting and Data System  (BI-RADS) mammographic breast density levels of D (extremely dense) were recruited and randomized to receive either ASA 160 mg/day (n=27) or no treatment (n=26). The final analyses included 25 women in the ASA group and 24 women in the no-treatment group.

A Significant Decrease in 20 Proinflammatory Protein Levels Observed

After 6 months of ASA treatment, a panel of 92 inflammatory proteins was analyzed. Of these, 20 demonstrated significantly decreased levels after false discovery rate (FDR) correction in breast tissue. The magnitude of changes for these 20 proteins ranged from 9% to 18%. None of the altered proteins in breast tissue showed any changes in abdominal subcutaneous fat. No changes in protein levels were observed in breast tissue or abdominal subcutaneous fat of participants in the no-treatment group after 6 months. 

An additional 17 proteins demonstrated altered levels in breast tissue after 6 months of ASA,  with a p < 0.05, but the changes did not remain statistically significant after FDR correction. In the no-treatment group, two proteins showed decreased levels in breast tissue after 6 months with a p < 0.05, but not after FDR correction. 

Low-Dose ASA Reduced Breast Tissue Perfusion but Not Density

On measuring perfusion, the fraction of contrast agent in the wash-in phase decreased significantly compared to baseline after low-dose ASA as well as no treatment (p < 0.001). However, significantly more participants in the ASA group demonstrated a decreased wash-in fraction than the no-treatment group (p < 0.05). The wash-out fraction decreased significantly in the ASA group (p < 0.001) but did not change in the no-treatment group. The wash-out rate correlated significantly with the angiogenic factor VEGF. 

Breast density was analyzed with the continuous MRI measure of lean tissue fraction before and after 6 months of ASA treatment or no treatment. No differences were observed in either group. Moreover, no significant changes were observed in the proton density fat fraction. These findings suggest that there were no significant structural changes in breast tissue. 

Low-Dose ASA Decreased R2 Relaxation in Fibroglandular Tissue

In the fibroglandular tissue segment, relaxation in R2 demonstrated a slight but significant decrease (p < 0.05) after 6 months of ASA treatment, whereas relaxation parameters did not change significantly in the no-treatment group. R1, R2, or PD relaxation properties showed no changes in fat tissue, duct, or blood vessel segments.    

Source:

Lundberg, P., Abrahamsson, A., Kihlberg, J., Tellman, J., Tomkeviciene, I., Karlsson, A., Wiberg, M. K., Warntjes, M., & Dabrosin, C. (2024). Low-dose acetylsalicylic acid reduces local inflammation and tissue perfusion in dense breast tissue in postmenopausal women. Breast Cancer Research, 26(1). https://doi.org/10.1186/s13058-024-01780-2 

Trastuzumab, marketed under the brand name Herceptin, is a standard therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The drug DRL_TZ, a potential trastuzumab biosimilar to Herceptin, was developed to improve affordability. 

A randomized, double-blind study conducted by the drug manufacturer evaluated the efficacy, safety, pharmacokinetics, and immunogenicity of DRL_TZ versus Herceptin (reference medicinal product [RMP]) plus paclitaxel in HER2-positive metastatic breast cancer patients. The study’s results were published in the journal JCO Global Oncology. 

Participant Characteristics

A total of 164 patients were randomized (1:1) to receive either DRL_TZ or RMP. An additional 44 patients were recruited to the DRL_TZ arm, resulting in 126 patients (82 randomized + 44 non-randomized) in the “pooled test arm”. Demographics and baseline clinical characteristics were balanced between the arms. Most patients were Asian (90.2%).

Statistically Comparable Best Overall Response Rates Observed 

In the intention-to-treat (ITT) population, by week 25, complete response was observed in five patients in the DRL_TZ arm and one patient in the RMP arm, whereas a partial response was observed in 40 patients in the DRL_TZ arm and 37 in the RMP arm. Two patients in the DRL_TZ arm and three in the RMP arm showed stable disease. Similar results were observed in the full analysis set/modified ITT (FAS/mITT) and per protocol (PP) populations.

Primary efficacy analysis revealed the best overall response rate (ORR) of 91.9% (93.3% confidence interval: 83.2–96.3) in the DRL_TZ arm (n=62) and 82.1% (93.3% CI: 72.0–89.1) in the RMP arm (n=67) in the PP population; the between-arm difference in proportion was 9.8%. The ITT and FAS/mITT populations showed similar results.

Comparable Progression-Free Survival and Disease Control Rate Observed 

Progression-free survival (PFS) at 6 months was observed in 85.4% of patients in the DRL_TZ arm and 70.9% in the RMP arm in the PP population; the between-arm difference was 14.5%. The disease control rate (DCR) in the PP population was 96.8% in the DRL_TZ arm and 91% in the RMP arm; the between-arm difference was 5.7%. Overall comparable data was observed in the randomized and pooled DRL_TZ patients for best ORR, PFS, and DCR.  

Similar Safety Profiles

Treatment-emergent adverse events (TEAEs) were reported in 155 patients, including 78 (95.1%) in the DRL_TZ arm and 77 (93.9%) in the RMP arm. The most common TEAEs were anemia, asthenia, alopecia, diarrhea, peripheral neuropathy, leukopenia, pyrexia, cough, and pain. In total, 34 serious adverse events (SAEs) were reported in 23 patients, including 20 SAEs in 15.9% of DRL_TZ arm patients and 14 in 12.2% of RMP arm patients. There were three fatal events (not related to the study drug). Grade ≥3 TEAEs occurred in 36.6% and 40.2% of patients in the DRL_TZ and RMP arms, respectively. Six, three, and ten patients experienced cardiac toxicity in the DRL_TZ, RMP, and pooled test arms, respectively.

Comparable Pharmacokinetics and Immunogenicity

The trastuzumab pharmacokinetic parameters were comparable between the treatment arms, with no statistically significant differences. The incidence of antidrug antibodies was low and comparable in both arms, with no neutralizing antidrug antibodies observed.

Source:

Reddy, N. C., Reddy, P., Ranpura, A., Maharaj, N., Arora, R. S., Mamillapalli, G., Adhav, A., Diwan, A. K., Manikhas, A., & Krasnozhon, D. (2024). Efficacy, safety, pharmacokinetics, and immunogenicity of DRL-Trastuzumab versus herceptin in human epidermal growth factor receptor 2–Positive metastatic breast cancer: a randomized controlled trial. JCO Global Oncology, 10. https://doi.org/10.1200/go.22.00328 

Breast cancer is among the five most common causes of cancer mortality. Despite improvements in its treatment, 5-year survival rates of metastatic breast cancer (mBC) still remain low, at 30%. There are three predominant sub-types of breast cancer, including hormone receptor-positive, hormone receptor-positive, human epidermal growth factor receptor(HER)2-overexpressing, and triple-negative breast cancer. The HER2-overexpressing sub-type is treated with anti-HER2 in combination with taxanes as the standard first-line treatment. 

Trastuzumab deruxtecan (T-DXd), a third-generation antibody–drug conjugate (ADC), offers promise due to its high drug-to-antibody ratio and potent cytotoxic payload. The phase 2 DAISY trial aimed to evaluate the effectiveness of T-DXd in patients with mBC across different HER2 expression levels in order to more fully understand its mechanism of action and resistance mechanisms. The findings of the study were published in the journal Nature Medicine.

T-DXd Response Associated Not Just to HER2 Expression

The trial enrolled 186 patients with mBC, stratifying them into cohorts based on HER2 status. Cohort 1 consisted of patients with HER2-overexpressing mBC, while cohort 2 comprised patients with HER2-low, and cohort 3 comprised patients with HER2-non-expressing mBC. The primary endpoint was the confirmed objective response rate (ORR), which was significantly higher in cohort 1 (70.6%) compared to cohorts 2 (37.5%) and 3 (29.7%). Additionally, patients in cohort 1 exhibited a longer median progression-free survival (PFS) of 11.1 months, compared to that of cohort 2 (6.7 months) and cohort 3 (4.2 months). Notably, patients in cohort 1 demonstrated a clinical benefit rate of 85.3%.

The study further explored HER2 expression patterns and their correlation with treatment responses. Spatial distribution analysis revealed a significant association between cluster 6, characterized by low HER2 staining and moderate cell density, and non-response in HER2-overexpressing tumors. However, no such association was found in HER2-low tumors. Moreover, no significant predictive value of HER2 expression levels was observed in HER2-non-expressing tumors. 

The mechanisms of action of T-DXd were explored, focusing on its distribution and impact on the tumor microenvironment. T-DXd uptake was correlated with HER2 expression. Furthermore, while T-DXd did not significantly alter the immune microenvironment overall, it decreased programmed death-ligand 1 (PD-L1) expression in HER2-overexpressing tumors, possibly due to its cytotoxic effects.

Investigation into resistance mechanisms revealed potential genomic alterations associated with primary and secondary resistance. Whole-exome sequencing identified ERBB2 amplifications and hemizygous deletions as potential indicators of resistance. Additionally, SLX4 mutations were detected in resistant tumors, implicating its role in mediating T-DXd resistance. Cell viability assays further supported SLX4’s involvement in resistance, suggesting its potential as a therapeutic target.

The Bottom Line

The study found that T-DXd response was related to HER2 expression. It was also found that higher T-DXd efficacy in HER2-overexpressing mBC. It also found that HER2 expression was lower in resistant cases. This confirms evidence from a previous study that the HER2 quantitative continuous score (QCS) could be used to predict outcomes with T-DXd use. However, the study also found modest activity of T-DXd in patients who did not express HER2, suggesting that drug efficacy is also related to other mechanisms independent of HER2. These findings provide a rationale for ongoing trials in mBC patients with ultra-low HER2.

Source:

Mosele, F., Deluche, É., Lusque, A., Bescond, L. L., Filleron, T., Pradat, Y., Ducoulombier, A., Pistilli, B., Bachelot, T., Viret, F., Lévy, C., Signolle, N., Alfaro, A., Tran, D. T. N., Garberis, I., Talbot, H., Christodoulidis, S., Vakalopoulou, M., Droin, N., . . . Varga, A. (2023). Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial. Nature Medicine, 29(8), 2110–2120. https://doi.org/10.1038/s41591-023-02478-2 

Trastuzumab deruxtecan (T-DXd), a human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugate, is currently approved for treating HER2-expressing breast and gastric cancers and HER2-mutant non-small cell lung cancer. 

An open-label phase II study in the Journal of Clinical Oncology assessed the efficacy and safety of T-DXd in patients with locally advanced, metastatic, or unresectable HER2-expressing solid tumors.

Study Population

The study comprised 267 patients. The median age was 62 years. The patients had received a median of two lines of prior therapy, with 40.8% having received ≥ three lines, and 14.2% having received prior HER2 therapy. The median follow-up duration was 12.75 months.

Substantial Clinical Benefit in Patients With HER2-Expressing Solid Tumors

Of the 267 patients, 99 (37.1%) had a confirmed objective response. Investigator-assessed objective response rates (ORRs) were 57.5% for endometrial, 50.0% for cervical, 45.0% for ovarian, 39.0% for bladder, 22.0% for biliary tract, 4.0% for pancreatic cancers, and 30.0% for other tumors. 

Among the 75 participants with centrally-confirmed HER2 immunohistochemistry (IHC) 3+ expression, ORRs were 84.6% for endometrial, 75.0% for cervical, 63.6% for ovarian, 56.3% for bladder, 56.3% for biliary tract, 0% for pancreatic cancers, and 44.4% for other tumors.

Responses were observed in patients who received (36.8%) or did not receive (37.4%) prior HER2 therapy. An independent central review demonstrated that 37.5% (n=100) of patients had a confirmed ORR across all tumor types, whereas the proportions by cohort were 57.5% for endometrial, 37.5% for cervical, 42.5% for ovarian, 41.5% for bladder, 26.8% for biliary tract, 12.0% for pancreatic cancers, and 35.0% for other tumors.

Durable Clinical Activity and Significant Survival Benefits

The investigator-assessed median duration of response (DOR) was 11.3 months across all cohorts. The median DOR was not reached in the endometrial cancer cohort. Among HER2 subgroups, patients with IHC 3+ demonstrated the longest median DOR (22.1 months).

The investigator-assessed median progression-free survival (PFS) was 6.9 months, ranging from 3.2 months in pancreatic cancer to 11.1 months in endometrial cancer. Among HER2 subgroups, IHC 3+ patients demonstrated the longest median PFS (11.9 months).

The median overall survival (OS) was 13.4 months across all cohorts, ranging from 5.0 months in pancreatic cancer to 26.0 months in endometrial cancer. Among HER2 subgroups, IHC 3+ patients demonstrated the longest median OS (21.1 months).

Safety Was Consistent With the Established Safety Profile

Grade ≥1 drug-related adverse events (AEs) were observed in 84.6% of patients, with the most common being nausea, anemia, diarrhea, vomiting, and fatigue. Grade ≥3 drug-related AEs were observed in 40.8% of patients, with neutropenia and anemia being the most common. Serious drug-related AEs occurred in 13.5% of patients. Drug-related AEs led to treatment discontinuation in 8.6% of patients and dose reduction in 20.2% of patients. Drug-related AEs resulted in the deaths of four patients. Adjudicated drug-related interstitial lung disease/pneumonitis events occurred in 10.5% of patients, with one grade 3 event and three fatal cases.

Source:

Meric‐Bernstam, F., Makker, V., Oaknin, A., Oh, D., Banerjee, S., González-Martín, A., Jung, K. H., Ługowska, I., Manso, L., Manzano, A., Melichar, B., Siena, S., Stroyakovskiy, D., Fielding, A., Ma, Y., Puvvada, S. D., Shire, N. J., & Lee, J. (2024). Efficacy and safety of trastuzumab deruxtecan in patients with HER2-Expressing solid tumors: Primary results from the DESTINY-PanTumor02 Phase II trial. Journal of Clinical Oncology, 42(1), 47–58. https://doi.org/10.1200/jco.23.02005 

• Triple-negative breast cancer is characterized by its aggressive nature and lack of targeted treatments due to the absence of three key receptors.
• Ferroptosis is a form of cell death distinct from apoptosis and necrosis, driven by iron-dependent lipid peroxidation.
• This review identifies potential ferroptosis biomarkers and therapeutic targets, offering hope for improved triple-negative breast cancer prognosis and treatment strategies.
• The heterogeneity of ferroptosis in triple-negative breast cancer underlines the need for personalized therapeutic approaches.

Triple-negative breast cancer (TNBC) stands as a formidable challenge in oncology, known for its aggressive behavior and limited treatment options. Unlike other breast cancer subtypes, TNBC lacks estrogen, progesterone, and HER2 receptors, complicating its management and prognosis. 

Recent explorations into ferroptosis, a specialized form of cell death marked by iron-dependent lipid peroxidation, offer new insights. A systematic review, published in Cureus, delves into the nuanced relationship between ferroptosis and TNBC, aiming to uncover novel prognostic insights and therapeutic opportunities.

The Therapeutic Potential of Ferroptosis in TNBC

Ferroptosis represents a frontier of interest due to its unique mechanism of action and its potential impact on cancer biology, particularly in TNBC. The review synthesizes evidence suggesting that ferroptosis could act as both a prognostic marker and a therapeutic target. By analyzing the role of key regulators like glutathione peroxidase 4 (GPX4) and the crosstalk between ferroptosis and other cellular processes, researchers are beginning to piece together how manipulating this pathway could benefit TNBC patients.

Biomarkers and Targets: Paving the Way for Precision Medicine

One of the most interesting aspects of this review is its focus on identifying biomarkers and therapeutic targets related to ferroptosis. High levels of lipid peroxidation markers and specific proteins have been linked to ferroptosis induction in TNBC cells. These findings not only enrich our understanding of TNBC’s molecular landscape but also highlight potential avenues for intervention. The review emphasizes the importance of leveraging these biomarkers and targets to develop personalized treatment strategies.

Toward a New Paradigm in TNBC Treatment

The heterogeneity observed in ferroptosis responses among TNBC patients illustrates the complexity of this disease and the necessity for tailored therapeutic approaches. By integrating ferroptosis into the clinical management of TNBC, the review suggests a paradigm shift toward more effective, customized treatment regimens that could significantly improve patient outcomes.

A New Horizon for Clinicians and Researchers

By understanding the intricate dynamics between ferroptosis and TNBC, clinicians can better navigate the complexities of this aggressive cancer subtype, potentially leading to more effective treatments and prognostic models. As research progresses, the promise of ferroptosis modulators in clinical trials could indicate a future where TNBC can be managed more effectively, paving the way for improved patient care and outcomes. 

Source:

Khan, M. I., Sunkara, V., Yadav, M. P., Bokhari, S. F. H., Rehman, A., Maheen, A., Shehryar, A., Chilla, S. P., Nasir, M., Niaz, H., Choudhari, J., Anika, N. N., & Amir, M. (2024). Ferroptosis and Triple-Negative Breast Cancer: A Systematic Overview of Prognostic Insights and therapeutic potential. Cureus. https://doi.org/10.7759/cureus.51719