Real-World Clinical Outcomes With Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer.

PURPOSE: Sacituzumab govitecan (SG) is approved for the treatment of metastatic triple-negative breast cancer (mTNBC). We report the real-world clinical effectiveness and toxicity data of SG in patients with mTNBC. METHODS: A multi-institution retrospective study of patients with mTNBC treated with SG from January 2021 to May 2023 was conducted. Demographic and clinicopathologic variables were collected. Univariate and multivariate Cox regression models were used for survival analysis. RESULTS: A total of 115 patients were included. The median age at SG initiation was 60 years (range, 31-85). All patients were female; 73 (63.5%) were White and 31 (27.0%) were Black. The median number of previous therapies in the metastatic setting was two (range, 0-8). Sixty-one (56.0%) patients had primary refractory disease. Median relative dose intensity was 92% (range, 33%-100%). Grade 3 or higher adverse events (AEs) were seen in 50.9% of patients, which included neutropenia (35.7%), anemia (27.0%), vomiting (16.5%), fatigue (8.7%), and diarrhea (7.0%). Dose reductions and treatment discontinuation due to AEs were required in 51.3% and 13.2%, respectively. The objective response rate (ORR) was 27.8%. Median overall survival was 9.6 months (95% CI, 7.8 to 12.9) and median progression-free survival (PFS) was 4.8 months (95% CI, 3.6 to 5.9). In patients with human epidermal growth factor receptor 2 (HER2)-low mTNBC who received trastuzumab deruxtecan (T-DXd) after SG, the ORR to T-DXd was 34.8% and median PFS was 7 months (95% CI, 4.6 to 10.1). CONCLUSION: In a real-world cohort of heavily pretreated patients with mTNBC, SG retains its clinical activity. In a subgroup with HER2-low disease, T-DXd continues to demonstrate promising clinical activity after SG, supporting the use of sequential antibody-drug conjugates in this population.

Dendritic Cell Plasticity, Radiation, and Newton's Third Law.

Regulatory T cells protect damaged tissues but can undermine the effects of cancer treatments, including radiotherapy (RTx). Intratumoral immunostimulatory dendritic cells (type 1 conventional dendritic cells) respond to RTx with the production of regulatory T cell-attracting MDC/CCL22, undermining RTx effects. That effect can be reversed by EGFR-targeted IFNα, highlighting cDC1 plasticity and relevance as therapeutic targets. See related article by Bugno et al., p. 4450.

Comprehensive Assessment of Immune Phenotype and Its Effects on Survival Outcomes in HER2-Low versus HER2-Zero Breast Cancer.

Background: The understanding of molecular characteristics of HER2-low breast cancer is evolving since the establishment of trastuzumab deruxtecan. Here, we explore the differences in expression patterns of immune-related genes in the tumor immune microenvironment (TME) and survival between HER2-low and HER2-zero breast cancers. Methods: Comprehensive genomic and immune profiling, including RNA-seq gene expression assessment of 395 immune genes, was performed on FFPE samples from 129 patients with advanced HER2-negative (immunohistochemistry (IHC) 0, 1+ or 2+ with negative ERBB2 amplification by in-situ hybridization) breast cancer. Both estrogen receptor (ER) and HER2 statuses were obtained from available pathology reports. mRNA expressions of immune biomarkers, except for PD-L1 IHC and TMB, were derived from RNA-seq. Statistical comparisons were performed using the Kruskal-Wallis or Wilcoxon Rank-Sum test or the two-sample test for equality of proportions with continuity correction (p≤0.05 for significance). Survival differences were calculated using Kaplan-Meier analysis (p≤0.05 for significance). Results: There were no significant differences in mRNA expressions of immune-related genes between HER2-low and HER2-zero breast cancers. However, HER2-low breast cancers were associated with a higher proportion of ER-positivity. When ER was analyzed along with HER2, we observed a significantly higher tumor immunogenic signature (TIGS) expression in HER2-zero/ER-negative tumors than in HER2-low/ER-positive tumors (p=0.0088). Similarly, lower expression of PD-L1 and T cell immunoglobulin and ITIM domain (TIGIT) mRNA was observed in HER2-low/ER-positive tumors when compared to HER2-zero/ER-negative tumors (p=0.014 and 0.012, respectively). Patients with HER2-low tumors had a longer median OS than those with HER2-zero tumors (94 months vs 42 months, p=0.0044). Conclusion: Patients with HER2-low breast cancer have longer survivals yet display no differences in immune-related gene expression when compared to those with HER2-zero cancers. The differences in survival can be attributed to the higher rate of ER-positivity seen in HER2-low breast cancers, compared to HER2-zero tumors.

Potential association of SULT2A1 and ABCG2 variant alleles with increased risk for palbociclib toxicity.

Aim: This study evaluated associations between CYP3A4*22 and variants in other pharmacogenes (CYP3A5, SULT2A1, ABCB1, ABCG2, ERCC1) and the risk for palbociclib-associated toxicities.Materials & methods: Two hundred cancer patients who received standard-of-care palbociclib were genotyped and associations with toxicity were evaluated retrospectively.Results: No significant associations were found for CYP3A4*22, CYP3A5*3, ABCB1_rs1045642, ABCG2_rs2231142, ERCC1_rs3212986 and ERCC1_rs11615. Homozygous variant carriers of SULT2A1_rs182420 had higher incidence of dose modifications due to palbociclib toxicity (odds ratio [OR]: 4.334, 95% CI: 1.057-17.767, p = 0.042). ABCG2_rs2231137 variant carriers had borderline higher incidence of grade 3-4 neutropenia (OR: 4.14, 95% CI: 0.99-17.37, p = 0.052).Conclusion: Once validated, SULT2A1 and ABCG2 variants may be useful to individualize palbociclib dosing to minimize toxicities and improve treatment outcomes.

[Box: see text].

Under-Representation and Under-Reporting of Minoritized Racial and Ethnic Groups in Clinical Trials on Immune Checkpoint Inhibitors.

PURPOSE: Minoritized racial/ethnic groups are historically under-represented in cancer clinical trials, which may be exacerbated in recent trials on immune checkpoint inhibitors (ICIs). We examined the representation and reporting of the racial/ethnic composition of participants in clinical trials on ICIs. METHODS: We examined English full-text trials on ICIs published from 2007 to 2022. Information on trial characteristics and racial/ethnic composition of participants was extracted from published papers or ClinicalTrials.gov. Differences in participation by publication year, ICI agent, and cancer site were analyzed. Enrollment-incidence ratio (EIR) was calculated to compare the proportion of minoritized racial/ethnic group patients in US-based trials against age-adjusted cancer incidence data available for the US population. An EIR > 1 signified over-representation, whereas an EIR <1 signified under-representation. RESULTS: Of the 471 trials examined, racial composition was unreported in 146 (31%), whereas Hispanic/Latinx ethnicity was unreported in 278 (59%). Only 30 (6%) trials reported race/ethnicity-specific results. In US-only trials (n = 174), White patients were over-represented (EIR, 1.20 [95% CI, 1.17 to 1.22]), whereas Hispanic/Latinx patients were the most under-represented (EIR, 0.35 [95% CI, 0.24 to 0.48]), followed by Black/African American patients (EIR, 0.66 [95% CI, 0.54 to 0.79]). Subgroup analyses consistently indicated over-representation of White patients across publication years (EIR, 1.19-1.24), ICI classes (EIR, 1.16-1.23), and cancer sites (EIR, 1.11-1.31), whereas Hispanic/Latinx patients were consistently under-represented. An upward trend of trial representation and reporting was observed for all minoritized racial/ethnic groups over time (trend P values ≤.05). CONCLUSION: Disparities in the representation and reporting of minoritized racial/ethnic groups persist in recent trials on ICIs, necessitating collaborative efforts for improved diversity and equitable cancer treatment access.

Detrimental Impact of Chemotherapy Dose Reduction or Discontinuation in Early Stage Triple-Negative Breast Cancer Treated With Pembrolizumab and Neoadjuvant Chemotherapy: A Multicenter Experience.

BACKGROUND: Pembrolizumab combined with neoadjuvant chemotherapy (NAC) is the current standard of care in early stage triple-negative breast cancer (TNBC) based on higher event-free survival and pathological complete response (pCR) in Keynote-522 (KN-522) clinical trial. However, this aggressive five-drug regimen is associated with increased risks for immune-related adverse events (irAEs). We investigated real-world clinical outcomes and toxicity of this regimen as well as factors predictive of pCR and irAEs. METHODS: We identified and abstracted data from 153 early-stage TNBC patients treated with the KN-522 regimen between July 1, 2021, and December 31, 2023, at 4 academic institutions in the U.S. Descriptive analysis was conducted, univariate and multivariate analyses were performed to identify factors associated with pCR and irAEs. RESULTS: The median age was 52 years (interquartile range, 42-60years), with 66% White and 24% Black patients with stage I/II (67%), node-negative disease (58%), grade 3 (86%) tumors, and ≥1 comorbidities (68%). Approximately 21% discontinued pembrolizumab, because of toxicity; ∼50% received a lower relative dose intensity (RDI) of chemotherapy (dose reduction or discontinuation). Of the 153 patients, 99 (64.7%) achieved pCR and 83 (54%) experienced an irAE, with 18 (12%) having ≥ grade 3 irAE. The majority (90%) of the irAEs were observed during neoadjuvant phase. Stage I/II versus stage III disease (OR 1.55, CI 1.04-2.33, P = .03), age (OR 0.96, CI 0.93-0.99, P = .01) and full versus reduced RDI of NAC (OR 1.53, CI 1.04-2.26, P = .03) were associated with higher pCR rates on multivariate analyses. Fewer cycles of pembrolizumab were associated with a higher likelihood of irAEs (OR 1.52, CI 1.07-2.16, P = .02), likely explained by the early discontinuation and receipt of less than 8 cycles of pembrolizumab in patients who experienced irAEs. CONCLUSIONS: Our study validates the clinical efficacy of KN-522 regimen; however, we observed a higher incidence of irAEs (54%) in this real-world population. Lower stage and younger age were associated with higher likelihood of achieving pCR. Toxicity-related chemotherapy dose reduction or discontinuation was observed to adversely impact the likelihood of achieving pCR.

Social networks, social determinants, and mortality: Western New York Exposures and Breast Cancer study.

BACKGROUND: There are few studies of social support and other social determinants of health after breast cancer diagnosis and their associations with mortality; results have been inconclusive. Further, it is not known if observed associations are specific to women with breast cancer diagnosis or if associations would be similar among healthy women. METHODS: Women with incident, pathologically confirmed invasive breast cancer, stage I-IV (n = 1012), and healthy frequency age-matched participants (n = 2036) answered a social support questionnaire in prospective follow-up of a population-based case-control study, the Western New York Exposures and Breast Cancer Study. At interview, all participants were aged 35-79 years and resident of 2 counties in Western New York State. Mortality status was ascertained from the National Death Index. Participants were queried regarding the number of their close friends, frequency of seeing them, household size, household income, and marital status. Hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer-specific mortality (breast cancer women only) and all-cause mortality were estimated. RESULTS: Lower household income was associated with higher all-cause mortality among women diagnosed with breast cancer (HR = 2.48, 95% CI = 1.24 to 4.97) and similarly among the healthy women (HR = 2.63, 95% CI = 1.25 to 5.53). Number and frequency of seeing friends, marital status, and household size were not associated with mortality, either among breast cancer patients or among healthy women. CONCLUSION: Among those diagnosed with breast cancer and healthy women, lower income was associated with more than twice the mortality. Marital status, household size, and number or frequency of meeting friends were not associated with survival.

Infiltration of Common Myeloid Progenitor (CMP) Cells is Associated With Less Aggressive Tumor Biology, Lower Risk of Brain Metastasis, Better Response to Immunotherapy, and Higher Patient Survival in Breast Cancer.

OBJECTIVE: To investigate the clinical relevance of common myeloid progenitor (CMP) cells in breast tumor microenvironment (TME). BACKGROUND: The role of rare cells in TME is less studied. In Silico transcriptomic analyses of real-world data enable us to detect and quantify rare cells, including CMP cells. METHODS: A total of 5176 breast cancer (BC) patients from SCAN-B, METABRIC, and 5 single-cell sequence cohorts were analyzed using the xCell algorithm. The high group was defined as more than two-thirds of the CMP scores in each cohort. RESULTS: CMP cells consist of 0.07% to 0.25% of bulk breast tumor cells, more in estrogen receptor-positive (ER+) compared with triple-negative (TN) subtype (0.1% to 0.75%, 0.18% to 0.33% of immune cells, respectively). CMP cells did not correlate with any of the myeloid lineages or stem cells in TME. CMP infiltration was higher in smaller tumors, with lower Nottingham grade, and in ER+/HER2- than in TNBC consistently in both SCAN-B and METABRIC cohorts. High CMP was significantly associated with a lower risk of brain metastasis and with better survival, particularly in ER+/HER2-. High CMP enriched epithelial-to-mesenchymal transition and angiogenesis pathways, and less cell proliferation and DNA repair gene sets. High CMP ER+/HER2- was associated with less immune cell infiltration and cytolytic activity ( P <0.001). CMP infiltration correlated with neoadjuvant chemoimmunotherapy response for both ER+/HER2- and TNBC in the ISPY-2 cohort (AUC=0.69 and 0.74, respectively). CONCLUSIONS: CMP in BC is inversely associated with cell proliferation and brain metastasis, better response to immunotherapy, and survival. This is the first to report the clinical relevance of CMP infiltration in BC.

Targeting the tumor microenvironment to improve clinical outcomes in triple negative breast cancer patients and bridge the current disparity gap.

Triple negative breast cancer (TNBC) is a heterogenous disease that disproportionately affects Black women. TNBC outcomes among Black women are dismal secondary to multiple factors, such as poor healthcare accessibility resulting in delays in diagnosis, and aggressive disease biology in addition to a pro-tumor immune microenvironment (TME). Black women with breast cancer exhibit elevated levels of serum pro-inflammatory cytokines, and a pro-tumorigenic TME with higher immunosuppressive regulatory T cells (Tregs), M2 macrophages and exhausted CD8+ T cells. We have shown that the combined use of toll-like receptor 3 (TLR3) ligands with interferon-α (chemokine modulation: CKM) is able to enrich the tumor with CD8+ T cells, while not increasing immunosuppressive cells. Recent clinical trials have revealed the efficacy of immune checkpoint inhibitors (ICI) in rejuvenizing exhausted CD8+ T cells. We hypothesize that strategies to modulate the TME by enriching chemokines that attract CD8+T cells followed by reversal of CD8+ T cell exhaustion (ICI), when added to standard treatment, could potentially improve clinical outcomes, and mitigate the racial disparities in TNBC outcomes between Black and White Women.

Epidemiology of early vs late recurrence among women with early stage estrogen receptor-positive breast cancer in the Pathways Study.

BACKGROUND: Relatively little is known about the differences in prognostic factors for early vs late recurrence among women with early stage estrogen receptor-positive breast cancer. METHODS: We analyzed factors related to early (<5 years) vs late (≥5 years) recurrence in 2992 women with stage I-IIB estrogen receptor-positive breast cancer in the Pathways Study, a prospective cohort of women with breast cancer enrolled between 2006 and 2013, with ascertainment of recurrence and death through December 2021. RESULTS: After a median follow-up of 13.3 years, 341 (13.8%) women had recurrences, including 181 (53.7%) with late recurrence. Higher stage and grade were associated with recurrence regardless of timing, whereas progesterone receptor negativity was associated with early but not late recurrence. Receipt of endocrine therapy was associated with reduced risk of overall recurrence, but the length of endocrine therapy was not statistically significant in multivariable models. Minoritized racial and ethnic groups, including Asian, Black, and Hispanic women, had higher risk of early but not late recurrence compared to non-Hispanic White women. The trend of higher risk of early recurrence among these groups remained after adjustment for clinical, demographic, and socioeconomic factors but was statistically significant only in Asian women. CONCLUSIONS: Our study revealed potentially important distinctions for early vs late recurrence, including the associations with progesterone receptor negativity and self-identified race and ethnicity. Possible higher risk of early recurrence among Asian, Black, and Hispanic women provides novel evidence for the existence of disparities in cancer outcomes, even within the breast cancer subtype indicative of generally good prognosis.

Immunologic Factors Associated with Differential Response to Neoadjuvant Chemoimmunotherapy in Triple-Negative Breast Cancer.

Background: KEYNOTE-522 resulted in FDA approval of the immune checkpoint inhibitor pembrolizumab in combination with neoadjuvant chemotherapy for patients with early-stage, high-risk, triple-negative breast cancer (TNBC). Unfortunately, pembrolizumab is associated with several immune-related adverse events (irAEs). We aimed to identify potential tumor microenvironment (TME) biomarkers which could predict patients who may attain pathological complete response (pCR) with chemotherapy alone and be spared the use of anti-PD-1 immunotherapy. Methods: Comprehensive immune profiling, including RNA-seq gene expression assessment of 395 immune genes, was performed on matched FFPE tumor samples from 22 stage I-III TNBC patients (14 patients treated with neoadjuvant chemotherapy alone (NAC) and 8 treated with neoadjuvant chemotherapy combined with pembrolizumab (NAC+I)). Results: Differential gene expression analysis revealed that in the NAC group, IL12B and IL13 were both significantly associated with pCR. In the NAC+I group, LCK and TP63 were significantly associated with pCR. Patients in both treatment groups exhibiting pCR tended to have greater tumor inflammation than non-pCR patients. In the NAC+I group, patients with pCR tended to have greater cell proliferation and higher PD-L1 expression, while in the NAC group, patients with pCR tended to have lower cancer testis antigen expression. Additionally, the NAC+I group trended toward a lower relative dose intensity averaged across all chemotherapy drugs, suggesting that more dose reductions or treatment delays occurred in the NAC+I group than the NAC group. Conclusions: A comprehensive understanding of immunologic factors could potentially predict pCR to chemotherapy alone, enabling the avoidance of the unnecessary treatment of these patients with checkpoint inhibitors.

Impact of environmental temperature on the survival outcomes of breast cancer: A SEER-based study.

BACKGROUND: Experimental evidence in tumor-bearing mouse models shows that exposure to cool, that is, sub-thermoneutral environmental temperature is associated with a higher tumor growth rate and an immunosuppressive tumor immune microenvironment than seen at thermoneutral temperatures. However, the translational significance of these findings in humans is unclear. We hypothesized that breast cancer patients living in warmer climates will have better survival outcomes than patients living in colder climates. METHODS: A retrospective population-based analysis was conducted on 270,496 stage I-III breast cancer patients, who were retrieved from the Surveillance, Epidemiology and End Results (SEER) over the period from 1996 to 2017. The average annual temperature (AAT) was calculated based on city level data from the National Centers for Environmental Information. RESULTS: A total of 270, 496 patients were analyzed. Temperature as assessed in quartiles. After adjusting for potential confounders, patients who lived in the 3rd and 4th quartile temperature regions with AAT 56.7-62.5°F (3rd quartile) and > 62.5°F (4th quartile) had a 7% increase in the OS compared to patients living at AAT < 48.5°F (1st quartile) (HR 0.93, 95% CI 0.90-0.95 and HR 0.93, 95% CI 0.91-0.96, respectively). For DSS, When comparing AAT quartiles, patients living with AAT in the range of 56.7-62.5°F and > 62.5°F demonstrated a 7% increase each in DSS after adjustment (HR 0.93, 95% CI 0.90-0.96 and HR 0.93, 95% CI 0.90-0.96). CONCLUSIONS: Higher environmental temperatures are associated with significantly better OS and DSS in breast cancer patients. Future research is warranted to confirm this observation using large datasets to elucidate the underlying mechanisms and investigate novel therapeutic strategies to minimize this geographic disparity in clinical outcomes.

Targeting beta-adrenergic receptor pathways in melanoma: how stress modulates oncogenic immunity.

The intricate pathways of the sympathetic nervous system hold an inherently protective role in the setting of acute stress. This is achieved through dynamic immunomodulatory and neurobiological networks. However, excessive and chronic exposure to these stress-induced stimuli appears to cause physiologic dysfunction through several mechanisms that may impair psychosocial, neurologic, and immunologic health. Numerous preclinical observations have identified the beta-2 adrenergic receptor (ß2-AR) subtype to possess the strongest impact on immune dysfunction in the setting of chronic stressful stimuli. This prolonged expression of ß2-ARs appears to suppress immune surveillance and promote tumorigenesis within multiple cancer types. This occurs through several pathways, including (1) decreasing the frequency and function of CD8 + T-cells infiltrating the tumor microenvironment (TME) via inhibition of metabolic reprogramming during T cell activation, and (2) establishing an immunosuppressive profile within the TME including promotion of an exhausted T cell phenotype while simultaneously enhancing local and paracrine metastatic potential. The use of nonselective ß-AR antagonists appears to reverse many chronic stress-induced tumorigenic pathways and may also provide an additive therapeutic benefit for various immune checkpoint modulating agents including commonly utilized immune checkpoint inhibitors. Here we review the translational and clinical observations highlighting the foundational hypotheses that chronic stress-induced ß-AR signaling promotes a pro-tumoral immunophenotype and that blockade of these pathways may augment the therapeutic response of immune checkpoint inhibition within the scope of melanoma.

Systemic infusion of TLR3-ligand and IFN-α in patients with breast cancer reprograms local tumor microenvironments for selective CTL influx.

BACKGROUND: Presence of cytotoxic T lymphocytes (CTL) in the tumor microenvironment (TME) predicts the effectiveness of cancer immunotherapies. The ability of toll-like receptor 3 (TLR3) ligands, interferons (IFNs) and COX2 inhibitors to synergistically induce CTL-attracting chemokines (but not regulatory T cell (Treg)-attractants) in the TME, but not in healthy tissues, observed in our preclinical studies, suggested that their systemic application can reprogram local TMEs. METHODS: Six evaluable patients (33-69 years) with metastatic triple-negative breast cancer received six doses of systemic chemokine-modulating (CKM) regimen composed of TLR3 ligand (rintatolimod; 200 mg; intravenous), IFN-α2b (20 MU/m2; intravenous) and COX2 inhibitor (celecoxib; 2×200 mg; oral) over 2 weeks. The predetermined primary endpoint was the intratumoral change in the expression of CTL marker, CD8α, in the post-CKM versus pre-CKM tumor biopsies. Patients received follow-up pembrolizumab (200 mg, intravenously, every 3 weeks), starting 3-8 days after completion of CKM. RESULTS: Post-CKM biopsies showed selectively increased CTL markers CD8α (average 10.2-fold, median 5.5-fold, p=0.034) and granzyme B (GZMB; 6.1-fold, median 5.8-fold, p=0.02), but not FOXP3 (Treg marker) relative to HPRT1 expression, resulting in the increases in average CD8α/FOXP3 ratio and GZMB/FOXP3 ratio. CKM increased intratumoral CTL-attractants CCL5 and CXCL10, but not Treg-attractants CCL22 or CXCL12. In contrast, CD8+ T cells and their CXCR3+ subset showed transient decreases in blood. One clinical response (breast tumor autoamputation) and three stable diseases were observed. The patient with clinical response remains disease free, with a follow-up of 46 months as of data cut-off. CONCLUSIONS: Short-term systemic CKM selectively increases CTL numbers and CTL/Treg ratios in the TME, while transiently decreasing CTL numbers in the blood. Transient effects of CKM suggest that its simultaneous application with checkpoint blockade and other forms of immunotherapy may be needed for optimal outcomes.

Racial and Ethnic Disparity in Preoperative Chemosensitivity and Survival in Patients With Early-Stage Breast Cancer.

Importance: It remains unclear what survival benefit is associated with preoperative chemosensitivity after receiving neoadjuvant chemotherapy (NACT) among patients with resectable breast cancer from diverse racial and ethnic backgrounds. Objective: To investigate racial and ethnic disparities in chemosensitivity and association with survival in patients with early-stage breast cancer. Design, Setting, and Participants: This retrospective cohort study queried data from the National Cancer Database (NCDB) between calendar years 2010 and 2018. Participants included patients with breast cancer with clinical stage I to III disease treated with NACT. Preoperative chemosensitivity was defined as very sensitive (ypT0N0), sensitive (pathologic TNM stage less than clinical stage, excluding ypT0N0), and refractory (pathologic stage greater than or equal to clinical stage). Data were analyzed in November 2022. Exposure: Receipt of NACT and clinicopathologic and treatment factors contributing to racial and ethnic disparities in survival. Main Outcomes and Measures: Overall survival of patients from diverse racial and ethnic backgrounds who received NACT. Results: This study included 103 605 patients (median age, 53 [IQR, 44-62] years, 99.5% [n = 103 060] women, and 68.7% [n = 71 203] White race). Among them, breast cancer was refractory in 43.2% (n = 44 796), sensitive in 34.4% (n = 35 638), and very sensitive in 22.4% (n = 23 171) of patients. In the hormone receptor-positive ERBB2 negative (formerly HER2 negative) group, patients had more refractory disease regardless of race or ethnicity (all races and ethnicities refractory: 54%-59%; P < .001). Among ERBB2 positive disease, Black patients had a lower percentage of very sensitive disease (32% vs 37%-40%; P < .001) and among triple-negative breast cancer, more refractory disease was seen among Black patients compared with other races and ethnicities (38% vs 30%-35%; P < .001). In refractory (hazard ratio [HR], 1.53; 95% CI, 1.47-1.60; P < .001) and sensitive (HR, 1.25; 95% CI, 1.17-1.33; P < .001) disease, Black patients had a higher mortality risk compared with White patients in the overall cohort. Asian patients had a lower mortality risk compared with White patients in refractory (HR, 0.71; 95% CI, 0.63-0.80; P < .001), sensitive (HR, 0.58; 95% CI, 0.49-0.69; P < .001), and very sensitive (HR, 0.60; 95% CI, 0.43-0.82; P < .001) disease groups in the overall cohort. Conclusions and Relevance: In this cohort study, Black patients had a higher mortality risk compared with White patients among those with residual disease after NACT. This highlights the need for personalized treatment strategies for Black patients to help them attain pathologic complete response.

Oncotype Dx Score, HER2 Low Expression, and Clinical Outcomes in Early-Stage Breast Cancer: A National Cancer Database Analysis.

BACKGROUND: The interaction between HER2-low expression, oncotype recurrence score (RS), and their influence on the prognosis of HR+/HER2- breast cancer (BC) is not very well studied. METHODS: We conducted a retrospective cohort study of patients diagnosed with resectable HER2-low and HER2-zero BC from the National Cancer Database. The primary outcome was overall survival (OS), and the association of RS with the clinical outcomes in HR+/HER2- BC was analyzed as an exploratory endpoint. RESULTS: The distribution of RS was comparable between HER2-low and HER2-zero groups; however, the RSs of HER2-low tumors were more likely to be 16-25. Women with HER2-low tumors had longer 5-year OS than women with HER2-zero tumors in the HR-negative (84.3% vs. 83.9%; p < 0.001, HR: 0.87 (0.84-0.90), p < 0.001) but not in the HR-positive group (94.0% vs. 94.0%; p = 0.38, HR: 0.97 (0.95-0.99), p = 0.01). The survival advantage was observed in patients who received adjuvant/neoadjuvant chemotherapy (p-interaction (chemo vs. no chemo) < 0.001). Among those who received adjuvant chemotherapy in the group with higher RSs (26-100), those with HER2-low BC had higher 5-year OS than HER2-zero BC. CONCLUSIONS: Resectable HER2-low BC had a better prognosis than HER2-zero BC. Among those who received adjuvant chemotherapy in the higher oncotype RS group, those with HER2-low tumors had better survival.

Novel Biomarkers to Guide Immunotherapy De-Escalation in the Neoadjuvant Setting in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) has the highest incidence of disease recurrence and distant metastases among breast cancer subtypes, leading to significant rates of morbidity and mortality [...].

Effect of neighborhood deprivation index on breast cancer survival in the United States.

PURPOSE: To analyze the association between the Neighborhood Deprivation Index (NDI) and clinical outcomes of locoregional breast cancer (BC). METHODS: Surveillance, Epidemiology and End Results (SEER) database is queried to evaluate overall survival (OS) and disease-specific survival (DSS) of early- stage BC patients diagnosed between 2010 and 2016. Cox multivariate regression was performed to measure the association between NDI (Quintiles corresponding to most deprivation (Q1), above average deprivation (Q2), average deprivation (Q3), below average deprivation (Q4), least deprivation (Q5)) and OS/DSS. RESULTS: Of the 88,572 locoregional BC patients, 27.4% (n = 24,307) were in the Q1 quintile, 26.5% (n = 23,447) were in the Q3 quintile, 17% (n = 15,035) were in the Q2 quintile, 13.5% (n = 11,945) were in the Q4 quintile, and 15.6% (n = 13,838) were in the Q5 quintile. There was a predominance of racial minorities in the Q1 and Q2 quintiles with Black women being 13-15% and Hispanic women being 15% compared to only 8% Black women and 6% Hispanic women in the Q5 quintile (p < 0.001). In multivariate analysis, in the overall cohort, those who live in Q2 and Q1 quintile have inferior OS and DSS compared to those who live in Q5 quintile (OS:- Q2: Hazard Ratio (HR) 1.28, Q1: HR 1.2; DSS:- Q2: HR 1.33, Q1: HR 1.25, all p < 0.001). CONCLUSION: Locoregional BC patients from areas with worse NDI have poor OS and DSS. Investments to improve the socioeconomic status of areas with high deprivation may help to reduce healthcare disparities and improve breast cancer outcomes.

Adolescent and Young Adult (AYA) Oncology, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology focuses on considerations for the comprehensive care of AYA patients with cancer. Compared with older adults with cancer, AYA patients have unique needs regarding treatment, fertility counseling, psychosocial and behavioral issues, and supportive care services. The complete version of the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology addresses additional aspects of caring for AYA patients, including risk factors, screening, diagnosis, and survivorship.

A review of treatment options in HER2-low breast cancer and proposed treatment sequencing algorithm.

The expansion of the spectrum of human epidermal growth factor receptor 2 (HER2)-status to HER2-low, defined as HER2 expression of 1+ by immunohistochemistry (IHC) or 2+ by IHC without gene amplification, has made a major impact in the field of oncology. The HER2-low expression has emerged as a targetable biomarker, and anti-HER2 antibody-drug conjugate trastuzumab deruxtecan has shown significant survival benefit in pretreated metastatic HER2-low breast cancer (BC). With these recent data, the treatment algorithm for hormone receptor-positive and triple-negative BC needs to be reconsidered, as approximately half of these BCs are HER2-low. Although there are different therapeutic agents for hormone receptor-positive and hormone receptor-negative HER2-low BCs, there is no consensus regarding the sequencing of these agents. In this article, the treatment options for HER2-low BC are enumerated and a treatment sequencing algorithm based on the current clinical evidence proposed.