Matrix Medical Communications is a medical publishing company that produces the SABCS 2024 Conference Show Dailies. Below are summaries and links from content included in each of those e-Newsletters, featuring the latest presented research in breast cancer.
Jhaveri et al reported findings from the final data cutoff of the dose-expansion phase of the DESTINY-Breast08 trial on the safety and antitumor activity of trastuzumab deruxtecan plus capecitabine (T-DXd+CAPE) or capivasertib (T-DXd+CAPI) in human epidermal growth factor receptor 2 (HER2)–low metastatic breast cancer. Twenty patients received T-DXd+CAPE, and 40 received T-DXd+CAPI, with median age of 57.5 and 56.0 years, respectively. Fourteen patients (70%) in the T-DXd+CAPE arm had hormone receptor–positive (HR+) disease, and six patients (30%) had HR-negative (HR–) disease. All patients in the T-DXd+CAPI arm had HR– disease. Among those with HR negativity, first-line chemotherapy for metastatic breast cancer was reported in five patients (83.3%) in the T-DXd+CAPE arm and 18 patients (45.0%) in the T-DXd+CAPI arm. First-line hormonal therapy (with or without targeted therapy) was reported in nine patients (64.3%) with HR+ disease in the T-DXd+CAPE arm. Median T-DXd treatment duration was 11.1 months in the T-DXd+CAPE arm and 6.2 months in the T-DXd+CAPI arm. Median treatment duration was seven months for CAPE and 5.5 months for CAPI. Grade 3 or higher adverse events were reported in 27 patients (67.5%) in the T-DXd+CAPI group and 11 patients (55.0%) in the T-DXd+CAPE group. Two patients in the T-DXd+CAPE arm and 13 in the T-DXd+CAPI arm had serious AEs. Safety data were consistent with the known safety profiles of each medication. In both arms, objective response rate (ORR) was 60 percent. Median duration of response was not reached in the T-DXd+CAPE arm, compared to 7.1 months in the T-DXd+CAPI arm. The T-DXd+CAPE arm had a median progression-free survival (PFS) of 13.4 months, and median PFS was nine months in the T-DXd+CAPI arm. Overall survival data was immature for both groups. The 12-month survival rate was 78 and 92 percent in the T-DXd+CAPE and T-DXd+CAPI arms, respectively.
Here, researchers compared relapse patterns among patients with triple-negative breast cancer (TNBC) who did or did not achieve pathologic complete response (pCR). Among 898 patients with TNBC who received neoadjuvant therapy, 443 (49.3%) experienced pCR. Patients who achieved pCR had median tumor-infiltrating lymphocytes of 15 percent, compared to 10 percent for those who did not achieve pCR; this difference was significant. At a median follow-up of 4.6 years, 141 relapse-free survival (RFS) events occurred in the non-pCR group and 30 RFS events occurred in the pCR group. Patients who achieved pCR had a significantly longer five-year RFS rate, compared to those who did not achieve pCR (92.7% vs. 67.2%). Five-year cumulative incidence of distant metastasis and distant metastasis involving a visceral site were 15.4 and 10.6 percent, respectively. At five years, the incidence of distant metastasis was 4.1 percent in the pCR group and 25.8 percent in the non-pCR group, and the rate of distant metastasis involving a visceral site was 3.6 and 17.1 percent in the pCR and non-pCR groups, respectively; these differences were significant. The five-year cumulative incidence of central nervous system (CNS)–only relapse was similar between groups, at 2.6 and 2.3 percent in the pCR and non-pCR groups, respectively. A significantly smaller proportion of patients in the non-pCR group who experienced distant recurrence had visceral involvement, compared to those in the pCR group. Among patients with distant metastasis as a first event, the most common site of recurrence was CNS-only in the pCR group, at 58.8 percent, which was significantly greater than the non-pCR group (8.2%). The liver was the second most frequent site of distant recurrence among those who achieved pCR (29.4%), which did not significantly differ from patients who did not achieve pCR (26.4%).
Han et al compared the impact of breast surgery for invasive breast cancer and breast surgery for benign, prophylactic, or premalignant conditions on sexual functioning and wellbeing. Among 86 participants, 74 received surgery for invasive breast cancer and 12 received surgery for a noninvasive indication. Mean age was higher in the invasive breast cancer group versus the noninvasive indication group (50.1 vs. 45.5 years). Dyadic Adjustment Scale (DAS) scores indicated that both groups had good partner relations, with mean scores of 117.9 and 119.9 in the breast cancer and non-breast cancer groups, respectively. Mean World Health Organization-Five Wellbeing Index (WHO-5) scores did not significantly differ between groups, at 51.17 for the breast cancer group and 61.45 for the non-breast cancer group, and indicated that patients had good wellbeing. Combining the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS-R) cutoff scores, the rate of sexual dysfunction was increased in the breast cancer group, compared to the non-breast cancer group (55.4% vs. 16.7%). Among participants with a history of breast cancer, sexual dysfunction was highest among those who stopped endocrine therapy (ET; 60.0%), followed by those currently receiving ET (55.9%) and those who never received ET (52.4%). Mean FSFI score was 18.83 in the breast cancer group, compared to 23.47 in the non-breast cancer group, indicating worse sexual function in the former. Among ET subgroups, mean FSFI score was lowest among participants who ceased ET (15.51), followed by those currently receiving ET (17.67) and those who never received ET (21.4). Post-breast surgery sexual distress was more prevalent in the breast cancer group versus the non-breast cancer group, with mean FSDS-R scores of 24.0 and 10.9, respectively. In the breast cancer group, participants who stopped ET had a mean score of 34.89, those currently receiving ET had a mean score of 24.65, and those who never received ET had a mean score of 18.14.
Ten-year local recurrence rates among patients with ductal carcinoma in situ (DCIS) who experienced selective omission of re-excision due to having margins less than 2mm following breast-conserving surgery (BCS). This study included 468 patients with DCIS with a median age of 59 years. Most cases were unifocal (87.4%), and 90.6 percent of patients had pure DCIS without microinvasion. About half of patients had grade 3 disease. Re-excision occurred in 112 patients (23.9%). The majority of patients (81.0%) had a final margin status of 2mm or greater, followed by less than 1mm (8.3%), 1 to 1.9mm (7.9%), and on-ink (2.8%). A total of 94.4 percent of patients with margins less than 2mm had only one margin location less than 2mm; 36 patients had their only margin less than 2mm in the anterior/posterior site. Multifocality was significantly more frequent in patients with margins less than 2mm, compared to those with margins of 2mm or greater (20.2% vs. 10.8%). Overall, 83.3 percent of patients received adjuvant radiotherapy. At median follow-up of 10.9 years, the 10-year local recurrence rate was highest among patients with a final margin width of less than 1mm (including on-ink), at 23.0 percent, followed by those with a margin width of 1 to 1.9mm (8.8%) and 2mm or greater (5.9%). Margins less than 1mm were associated with a significantly increased risk of local recurrence, compared to margins 2mm or greater; significance was retained when adjusting for multifocality and when excluding patients with anterior/posterior margins less than 2mm. Margin width was not significantly associated with radiotherapy; however, patients with margins less than 2mm who did not receive radiotherapy experienced a numerically higher absolute rate of local recurrence.
Analyzing data from the Surveillance, Epidemiology, and End Results (SEER) program from 2010 to 2020, Aimalla et al assessed breast cancer incidence and survival among patients aged 20 to 49 years across different disease subtypes. Of 123,690 patients, 65.5 percent had HR+, HER2– disease, 20.5 percent had HER2+ disease, and 14 percent had HR–, HER2– disease. Breast cancer incidence was highest in patients aged 40 to 49 years, at 75.4 percent, followed by those aged 30 to 39 years (21.9%) and those aged 20 to 29 years (2.7%). Over half (55.85%) of cases were diagnosed form 2015 to 2020. Most patients were White (72.7%) and resided in urban areas (92.3%); 64.8 percent of patients were married, and 53.6 percent had an annual income below $75,000. Patients aged 20 to 29 years or 30 to 39 years experienced poorer survival outcomes than those aged 40 to 49 years across all disease subtypes, except the HR–, HER2– disease for those aged 20 to 29 years. OS HRs were 2.4 for HR+, HER2– disease and 1.36 for HER2+ disease for those aged 20 to 29 years (vs. 40–49 years). Among patients aged 30 to 39 years (vs. 40-49 years), OS HRs were 1.74, 1.11, and 1,08 for HR+, HER2–; HER2+; and HR–, HER2– disease, respectively. Patients with HR+, HER2– disease experienced significantly shorter OS from 2010 to 2014, compared to 2015 to 2020 (HR: 1.08). Across all disease subtypes, Asian race, higher income, residing in an urban area, being married, receipt of radiation therapy, and receipt of surgery were associated with improved OS. Compared to White patients, Asian and Native American patients experienced significantly improved OS, whereas Black patients had significantly poorer OS, across all disease subtypes. Receipt of chemotherapy was associated with longer OS in HER+ and HR–, HER2– subtypes. Higher disease stage was linked to worse OS regardless of disease subtype.
Researchers analyzed data from patients with newly diagnosed Stage I to III breast cancer to identify factors associated with alcohol intake. Among 734 patients, weekly alcohol intake of five drinks or more was reported in 176 patients at baseline (24%) and 137 (18.7%) at Year 4. There was a significant association between greater alcohol intake at baseline and greater intake at Year 4. Overall, total alcohol intake significantly decreased over time. Younger age at diagnosis, lack of radiotherapy, and presence of BRCA mutation were associated with higher alcohol intake at Year 4, according to univariate analysis. At baseline and Year 4, smoking showed a significant association with greater alcohol intake. More minutes of moderate and mild intensity exercise, greater Godin activity scores, and greater physical health at baseline and Year 4 were linked to higher alcohol intake. There was a positive association between Impact of Event Scale (IES-R) and Patient Health Questionnaire-2 (PHQ-2), which assessed post-traumatic and depressive symptoms, respectively, total scores at Year 2 and higher alcohol intake at Year 4. Additionally, intrusion, avoidance, and hyperarousal IES-R subscale scores were significantly associated with greater alcohol intake.
Among 36,670 patients under the age of 50 years who were diagnosed with breast cancer from 2008 to 2022, 4,344 (11.8%) underwent ovarian function suppression/ablation (OFS). A total of 19.3 percent of patients who underwent chemotherapy received OFS. The rate of OFS increased over time, from 6.6 percent pre-2016 to 24.8 percent in 2021; this increase was attributable to greater gonadotropin-releasing hormone agonist use, as the oophorectomy rate remained stable. Among patients treated with chemotherapy, OFS rose from 9.4 in 2008 to 45.9 percent in 2022. Receipt of chemotherapy and age of 18 to 34 years (vs. 45–49 years) were associated with increased OFS uptake. About half of all patients below the age of 45 years who received chemotherapy underwent OFS. The rate of bone mineral density testing within the first year of OFS was low, at 30.8 percent. A significantly greater proportion of patients who initiated OFS were on antidepressant medications in the first year, compared to those who did not initiate OFS (39.8% vs. 33.0%), though the rate of antidepressant initiation was comparable (12.6% vs. 12.7%). ET nonadherence in the first year was reported in 19.2 percent of patients receiving ET and OFS, compared to 16.9 percent of patients receiving ET alone; this difference was significant.
Researchers evaluated the impact of previous endocrine-based therapy response on outcomes with trastuzumab deruxtecan (T-DXd) treatment and physician’s choice of chemotherapy (TPC) among patients with hormone receptor–positive (HR+), human epidermal growth factor receptor 2 (HER2)–low or HER2-ultralow metastatic breast cancer. A total of 65.8 percent of patients in the intent-to-treat (ITT) population experienced progressive disease while on first-line endocrine therapy (ET) plus cyclin-dependent kinase 4/6 (CDK4/6) inhibitor and were included for time to progression (TTP) analysis; 124, 112, and 334 patients had a TTP of less than six months, 6 to 12 months, and over 12 months. Second-line T-DXd/TPC was most common among patients with TTP of less than six months (58.9%), followed by those with TTP of 6 to 12 months (23.2%) and TTP over 12 months (7.2%). Across all TTP subgroups, treatment with T-DXd resulted in longer PFS, compared to treatment with TPC. In the T-DXd arm, median PFS was 14, 13.2, and 12.9 months among the less than six months, 6 to 12 months, and over 12 months TTP subgroups, respectively, whereas in the TPC arm, median PFS was 6.5, 6.9, and 8.2 months, respectively. Similarly, the objective response rate (ORR) was increased in patients who received T-DXd (TTP <6 months: 67.7%; TTP 6–12 months: 60.0%; TTP >12 months: 59.5%), compared to those who received TCP (TTP <6 months: 25.4%; TTP 6–12 months: 28.8%; TTP >12 months: 33.1%). The T-DXd arm showed longer median duration of response among patients with TTP of less than six months (11.1 months), 6 to 12 months (13.7 months), and over 12 months (15.7 months), compared to the TCP arm (TTP <6 months: 7.3 months; TTP 6–12 months: 11.5 months; TTP >12 months: 11.1 months). Grade 3 or greater treatment-emergent adverse events (TEAEs) occurred at similar rates to the overall safety population across TTP subgroups.
In this study, Kudrik et al evaluated the rate of BRCA1/2 testing among 1,754 patients with newly diagnosed breast cancer and 2,638 patients diagnosed with metastatic breast cancer from 2021 to 2023. Median age was 49 years for patients with nonmetastatic disease and 66 years for those with metastatic disease. In both groups, most patients had HER2– disease. In the nonmetastatic group, 76 percent of patients were White, and 11 percent were Black/African American. In the metastatic group, these 72 percent of patients were White, and 15 percent were Black/African American. The rate of BRCA testing was lower in the nonmetastatic group, at 52 percent, compared to the metastatic group, at 71 percent. In the nonmetastatic group, there was a significant difference in the rate of BRCA testing among patients with HR–, HER2– disease (65%) and those with HR+, HER2– (48%) or HER2+ (47%) disease. BRCA testing rates also significantly differed by subtype in the metastatic group, with rates of 87, 67, and 59 percent among those with HR–, HER2–; HR+, HER2–; and HER2+ disease. Patients below the age of 65 years underwent BRCA testing at significantly increased rates than those aged 65 years or older (metastatic group: 81% vs. 63%; nonmetastatic group: 63% vs. 39%). BRCA testing rates did not significantly differ based on year of diagnosis or race (White vs. Black/African American).
In this study, researchers compared psychological resilience, distress, and perception of health among 50 patients with early breast cancer and 67 healthy controls. Outcomes were measured via the Depression, Anxiety, and Stress Scale (DASS-21); 36-Item Short-form Health Survey (SF-36), and Connor-Davidson RISC-25 Scale (CD-RISC-25). Mean age was 57.94 years in the early breast cancer group and 57.01 years in the control group. Seventy percent of patients with early breast cancer had Stage I disease, 24 percent had Stage II disease, and six percent had Stage III disease. Eighty-four percent of patients underwent breast-conserving surgery (BCS), 90 percent received antihormonal treatment, and 66 percent received adjuvant/neoadjuvant chemotherapy. CD-RISC-25 scores were significantly higher among patients with early breast cancer, suggesting that they had greater psychological resilience compared to controls. Scores for the SF-36 item concerning perceived change in general health compared to one year prior were lower in the early breast cancer group, compared to the control group. However, there were no significant differences in the four domains on physical and emotional health perception between groups. At one-year follow-up, patients with early breast cancer had significantly lower SF-36 physical functioning subscale scores but greater perceived general health compared to one year ago, compared to controls. CD-RISC-25 scores remained higher among patients with early breast cancer after one year. Compared to baseline measurements, at one-year follow-up, patients with early breast cancer exhibited lower scores for depression and distress and improved scores for social functioning and perception of general health compared to one year prior.
In this retrospective analysis, researchers aimed to identify predictors of nodal pCR in patients with Stage III inflammatory breast cancer. Data from 290 patients who received mastectomy and axillary lymph node dissection (ALND) were included. Median age was 52 years, and 60.3 percent of patients were postmenopausal. A total of 78.3 percent of patients were White, 5.9 percent were Black, and 12.4 percent were Hispanic. Most patients had node-positive disease (94.8%); 89.9 percent had ductal carcinoma, and 67.9 percent had high-grade tumors. The most common receptor subtype was HR+, HER2– (39.3%), followed by TNBC (24.8%); HR–, HER2+ (19.7%); and HR+, HER2+ (16/2%). Of patients with HR positivity, 52.1 percent had estrogen receptor–positive (ER+) disease and 36.2 percent had progesterone receptor–positive (PR+) disease; 9.3 and 10 percent had ER-low and PR-low disease, respectively. Ki-67 of 20 percent or greater was observed in 92.2 percent of patients. Patients with ER– disease had significantly greater odds of pCR compared to those with ER+ disease (50% vs. 23%), and similarly, PR negativity was linked to significantly higher likelihood of pCR, compared to PR positivity (46% vs. 19%). HER2+ disease and higher Ki-67 index were also associated with increased odds of pCR. Multivariate analysis showed that when HR status was a dichotomous variable, ER negativity was the strongest predictor of pCR, followed by non-White race. The rate of pCR was highest among non-White patients with ER– breast cancer (73.5%), and the pCR rate was lowest in patients with ER+/PR+ disease (16%). Further analysis determined that a cutoff point of less than 41 percent for ER and 35.7 percent or higher for Ki-67 were predictive of pCR.
Zhang et al reviewed 16 articles including 1,106 patients with triple-negative breast cancer (TNBC) to determine the prognostic significance of circulating tumor deoxyribonucleic acid (ctDNA). Eight articles including 361 patients were prospective observational studies, seven articles including 703 patients were clinical trials, and one article including 42 patients was a prospective case-control study. Nine studies (n=734) utilized next-generation sequencing (NGS) for ctDNA analysis, five studies (n=327) used polymerase chain reaction (PCR), and two studies (n=45) used other methods. There was an association between ctDNA positivity following neoadjuvant therapy and greater odds of recurrence in studies wherein recurrence was reported as a time-to-event outcome (hazard ratio [HR]: 3.79) and in studies that reported patient-level data (odds ratio [OR]: 6.59). Findings did not differ when stratifying patients based on ctDNA positivity before or after surgery. Furthermore, pooled log-HR data indicated that ctDNA positivity after neoadjuvant therapy was associated with poorer OS. Postneoadjuvant ctDNA positivity prior to surgery was also linked to decreased likelihood of achieving pathologic complete response (pCR). Higher odds of recurrence and shorter OS were associated with ctDNA positivity during or after treatment with adjuvant chemotherapy.
The DESTINY-Breast12 trial showed that trastuzumab deruxtecan (T-DXd) treatment was effective patients with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer with brain metastases (BM), with a 12-month progression-free survival (PFS) of 61.6 percent and central nervous system (CNS) objective response rate (ORR) of 71.7 percent. Researchers analyzed data from this Phase IIIb/IV trial to compare the impact of T-DXd treatment on health-related quality of life (HRQoL) and neurological function among the BM and non-brain metastases (NBM) cohorts. Median total treatment duration was 11.5 months in the BM cohort and 12 months in the NBM cohort. For the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30), a similar proportion of patients in the BM and NBM cohorts experienced clinically meaningful declines in cognitive functioning (45.3% and 44.9%, respectively). At baseline, a high proportion of patients with (86.6%) and without (91.9%) BM had neurological stability as per the Neurologic Assessment in Neuro-Oncology (NANO) scale. Of the 220 patients with BM who had neurological stability at baseline, 140 had neurological stability as their worst score at any point, and 80 experienced neurological progression as their worst score at any point during treatment; among 217 patients without BM, 172 and 45 had neurological stability and progression, respectively, as their worst score at any point during treatment. Sixteen (6.8%) and 25 (9.8%) patients in the NBM and BM cohorts, respectively, had neurological progression at baseline; six and seven of these patients, respectively, had neurological stability as their worst score at any time during treatment. These results showed that HRQoL and neurological function were preserved for most patients treated with T-DXd, regardless of BM status.
In this study, Zweigle et al assessed the factors related to genetic testing and counseling among patients with breast cancer residing in Eastern North Carolina. Data from patients with breast cancer who were referred for germline genetic testing from 2020 to 2023 were analyzed. Among 618 patients, 312 were referred due to a personal or family history of breast cancer, 187 (59.9%) of whom were Black and 114 (36.5%) of whom were White. Genetic counseling with testing was completed by 259 patients. Of 122 patients who tested positive for a germline variant, 23 (18.9%) had a pathogenic germline variant. Patients referred to genetic counseling due to a personal breast cancer history prior to starting treatment had a greater likelihood of completing genetic testing, compared to patients referred due to a family history of breast cancer. Among patients who received genetic testing, germline variant positivity was less common among patients with Medicare and Medicaid, compared to those with private insurance. Among those who tested positive for a variant, presence of a variant of undetermined significance (VUS) was more common among Black patients, compared to White patients. Patients who completed testing and were referred before treatment and those who were referred following treatment had lower odds of completing post-test counseling, compared to patients who were referred to screening and patients who were referred for a family history of breast cancer, respectively. The likelihood of attending follow-up was higher among unemployed versus employed patients.
Analyzing samples from female and male patients with breast cancer, reseaerchers found that hormone receptor–positive (HR+), HER2– disease was significantly more prevalent in male versus female patients (80.17% vs. 64.14%). Among patients with HR+, HER2– disease, BRCA2 and GATA3 alterations were observed in 10.64 and 22.68 percent of male patients, compared to 4.38 and 14.11 percent of female patients; these differences were significant. Female patients showed significantly increased frequency of TP53, ESR1, and CDH1 alterations, at 30.76, 13.62, and 17.43 percent, respectively, compared to male patients, at 3.45, 4.12, and 1.06 percent, respectively. High tumor mutational burden was significantly more common in female patients (9.08%) than in male patients (2.2%). High microsatellite instability/deficient mismatch repair and programmed death ligand-1 (PD-L1) positivity were comparable between groups. Androgen receptor (AR) ribonucleic acid (RNA) expression was decreased and AR protein positivity expression was increased in male patients, compared to female patients. The rate of fusion variant AR was similar between groups, at 1.04 percent for male patients and 3.19 percent in female patients. Male patients showed significantly higher expression of HLA-B and HLA-DQB2, whereas female patients had significantly increased expression of ABCC2 and stem cell–related genes.
About 30 to 40 percent of patients with HER2+ breast cancer harbor activating PIK3CA mutations, but their impact on metastatic breast cancer remains unclear. In this observational cohort study, researchers evaluated the impact of PIK3CA mutation on HER2+ metastatic breast cancer cases. Among 1,325 patients diagnosed from January 1, 2011, to September 31, 2022, 65.6 percent were White, and 11.2 percent were Black. Median age was 63 years. Most patients (76.8%) had HR+, HER2+ disease, and 23.2 percent had HR–, HER2+ disease. A total of 44.7 percent of patients harbored activating PIK3CA mutations. Other commonly observed alterations included BRCA1/2 (22.1%) and ESR1 (17.3%). The majority of patients (86.7%) underwent first-line treatment, with 49.9 percent of all patients receiving HER2-targeted therapy; 78.5 percent of patients with HR–, HER2+ breast cancer received HER2-targeted therapy, compared to 41.7 percent of those with HR+, HER2+ disease. Overall survival (OS) was numerically shorter in patients with PIK3CA-mutated disease, compared to those with PIK3CA-wildtype disease, at 50.6 and 57.1 months, respectively. In the subgroup of patients who received first-line HER2-targeted therapy, progression-free survival (PFS) and OS were significantly shorter with PIK3CA-mutated disease (9.0 and 45.8 months, respectively), compared to PIK3CA-wildtype breast cancer (11.1 and 61.3 months, respectively). Adjusted analysis showed a significant association between presence of activating PIK3CA mutation and poorer PFS and OS among those treated with first-line HER2-targeted therapy.
In this study, researchers assessed the impact of omitting surgical axillary staging in patients with early invasive breast cancer who underwent breast-conservation surgery (BCS). A total of 5,502 patients were randomized; after patient drop-out and exclusion, 4,858 patients were included in the per-protocol set, 962 in the no sentinel lymph node biopsy (SLNB) group and 3,896 in the SLNB group. Median follow-up was 73.6 months. In the overall group, median age at diagnosis was 62 years, and most patients had HR+ disease (98.5%) and pT1 stage tumors (78.6%). In the SLNB arm, the rate of adjuvant chemotherapy was 13.2 percent, which was significantly higher than the no SLNB arm (10.2%). Analysis of the per-protocol set demonstrated that no SLNB was not inferior to SLNB in terms of invasive disease-free survival (iDFS), with a hazard ratio of 0.91. Estimated five-year iDFS rates were similar between arms, at 91.9 and 91.7 percent in the no SLNB and SLNB arms, respectively. The overall rate of iDFS events was 10.8 percent. Occurrences of axillary recurrence and invasive contralateral breast cancer were slightly increased in the no SLNB group (1.0% each), compared to the SLNB group (0.3% and 0.6%, respectively). The rate of distant metastases was the same in both arms, at 2.7 percent. Secondary malignancies were reported in 3.3 percent of patients in the no SLNB arm and 3.9 percent of those in the SLNB arm. Estimated five-year OS was 98.2 percent in the no SLNB arm and 96.9 percent in the SLNB arm.
Among 164 patients aged 65 years or older with early breast cancer, 71 percent were considered vulnerable, nine percent were frail, and 20 percent were fit, according to the 43-item frailty index (43-FI). Vulnerable and frail patients tended to be older than fit patients. Ki-67 less than 20 percent was reported in 62 and 60 percent of vulnerable and frail patients, respectively, and 71 and 80 percent, respectively, had Grade 1 to 2 tumors. Among all groups, HR+, HER2– disease was the most common type of breast cancer. Only seven percent of frail patients received chemotherapy, compared to 33 and 63 percent of vulnerable and fit patients, respectively. Frail patients had a significantly shorter median OS, compared to fit patients (5.5 vs. 13.0 months). Vulnerable patients had a median OS of 9.8 months. Eight senescence-associated secretory phenotype (SASP)–related factors were associated with the 43-FI, with GDF15 showing the best association with frailty (area under the curve [AUC]: 0.88). Among vulnerable patients, high GDF15 expression was associated with significantly poorer median OS (7.8 months), compared to low GDF15 expression (11.6 months). Additionally, a senescence score model showed a positive association with prognosis.
Chan et al compared breast cancer treatment patterns and five-year overall survival (OS) outcomes among transgender/gender-diverse (TGD) patients and cisgender patients. Among 4,376,089 patients with breast cancer, 99.1 percent (n=4,338,258) were cisgender female, 0.9 percent (n=37,579) were cisgender male, and 0.006 percent (n=252) were TGD. Median age of TGD patients was 51 years, and 65.1 percent were non-Hispanic White. The majority of TGD patients were insured (85%) and had no medical comorbidities (78.6%). Hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) breast cancer was present in 52.5 percent of TGD patients, and 55.2 percent had node-negative disease. Median age was significantly younger (51 vs. 64 years) and presence of T2 tumors was significantly greater (24.2% vs. 17.5%) in the TGD cohort, compared to a random, unmatched, cisgender cohort (n=252). Disease stage was not significantly different between cohorts. Of 201 TGD patients with HR+ disease, 58.7 percent received endocrine therapy (ET); this was significantly lower than the proportion of cisgender patients treated with ET, which was 80.2 percent. The odds of being diagnosed at younger than 40 years of age were increased and the odds of receiving ET for HR+ breast cancer were decreased among TGD patients, compared to cisgender patients. When compared to a matched cisgender cohort (n=211), the rate of ET for HR+ disease was still significantly lower for TGD patients (58.5% vs. 67.6%), and this retained significance on regression analysis. TGD patients had a five-year OS rate of 84.6 percent, which was significantly lower than the 91.7-percent five-year OS rate among cisgender patients.
Findings from the DESTINY-Breast03 trial showed that trastuzumab deruxtecan (T-DXd) treatment conferred a 22-month improvement in median progression-free survival (PFS) in patients with HER2+ metastatic breast cancer with prior trastuzumab and taxane treatment, compared to trastuzumab emtansine (T-DM1). This study measured the impact of baseline and emergent genomic alterations on treatment efficacy. TP53, ERBB2, CDK12, and PIK3CA alterations were the most prevalent, found in 73, 61, 52, and 48 percent of patients, respectively. The frequency of HER2 amplification in circulating tumor deoxyribonucleic acid (ctDNA) was 56 percent. In the T-DXd arm, efficacy was comparable between those with high or low baseline median HER2 plasma copy number (CN); median PFS was 23.9 and 21.1 months for those with high and low HER2 plasma CN, respectively, at baseline, while objective response rate (ORR) was 87.1 and 81.4 percent, respectively. However, in the TDM-1 arm, PFS and ORR were shorter in patients with low baseline HER2 plasma CN (median PFS: 5.4 months, ORR: 35.6%), compared to those with high baseline HER2 plasma CN (median PFS: 9.7 months, ORR: 50.0%). HER2 activating mutation status did not significantly impact efficacy in either arm. Among patients treated with T-DXd, ORR and median PFS were similar regardless of presence or absence of PI3K pathway mutation (80.5% and 27.6 months vs. 82.1% and not evaluable, respectively). In contrast, patients in the T-DM1 arm with PI3K pathway mutations trended toward inferior ORR (33.3%) and PFS (median: 4.4 months), compared to those without such mutations (40.0% and 9.7 months, respectively). Patients with homologous recombination deficiency (HRD) positivity had comparable ORR to those with HRD negativity in the T-DXd arm (82.6% and 81.2%, respectively), while HRD positivity was linked to worse ORR in the T-DM1 arm (14.8% and 40.5%, respectively). Patients with HRD positivity experienced a median PFS of 12.4 and 2.8 months in the T-DXd and T-DM1 arms, respectively, whereas those with HRD negativity had a median PFS of 37.3 and 7.1 months in the T-DXd and T-DM1 arms, respectively.
In this study, Morganti et al analyzed data form the Young Women’s Breast Cancer Study to identify differences between breast cancer cases with and without germline BRCA mutation (gBRCAm) among patients aged 40 years or younger. Patients included in this analysis had Stage I to III HER– disease with known gBRCAm status. A total of 113 gBRCAm carriers (74 harboring BRCA1, 39 harboring BRCA2) and 226 matched controls were identified. Median age was 36 years in both groups. Stage II was the most common disease stage (46.3%), followed by Stage I (31%) and Stage III (22.7%). Triple-negative breast cancer (TNBC) and HR+ disease were present in 51.3 and 48.7 percent of patients, respectively. A significantly greater proportion of gBRCAm carriers underwent genetic testing prior to breast cancer diagnosis, compared to noncarriers. Tumor grade was significantly higher among gBRCAm carriers versus noncarriers. Among those with HR+ disease, gBRCAm carriers had a median recurrence score of 31 and noncarriers had median score of 19; this difference was significant. Receipt of chemotherapy was similar between groups, but noncarriers were more likely to receive ET for HR+ disease, compared to gBRCAm carriers. After adjustment, invasive disease-free survival (iDFS) and recurrence-free survival (RFS) were not significantly different between groups. However, there was a trend toward lower risk of five-year iDFS and RFS among gBRCAm carriers (82.4% and 84.4%, respectively), compared to noncarriers (78% and 79%, respectively). OS was comparable between groups, with five-year OS rates of 88.1 and 87 percent for gBRCAm carriers and noncarriers, respectively.
Researchers compared liquid biopsy with circulating tumor cells (CTCs) and tissue biopsy for determining HER2 status in metastatic breast cancer. Data from 143 patients with five or more CTCs were analyzed. Eighty-five percent of patients (n=121) had HER2– disease (HER2-low: n=46, HER2-0: n=36, not evaluable: n=39), and 15 percent (n=22) had HER2+ disease. Over 90 percent of patients in the HER2– and HER2+ groups had detectable HER2+ CTCs, but the proportion of HER2+ CTCs was increased in the HER2+ group; median CTC-to-HER2 ratio was significantly higher in the HER2+ group, at 0.30 versus 0.09 in the HER2– group. The HER2+ group also had a significantly increased CTC-to-HER2 ratio when compared to HER2-0 and HER2-low subgroups. Researchers conducted a receiver operating characteristic (ROC) curve analysis for HER2+ and CTC-to-HER2 ratio; area under the curve (AUC) was 0.7417, and 0.22 was the optimal cutoff, with a sensitivity and specificity of 63.64 and 82.64 percent, respectively. Positive and negative predictive values were 40 and 92.59 percent, respectively. For HER2-low and CTC-to-HER2 ratio, AUC was 0.5646 and optimal cutoff was 0.13. Sensitivity and specificity were 50 and 72.22 percent, respectively, and positive and negative predictive values were 69.7 and 53.06 percent, respectively.
Analyzing breast cancer cell models, Wang et al found that epithelial protein lost in neoplasm (EPLIN) knockdown led to active response of several proteins, notably apolipoprotein C3 (APOC3). There was a significant correlation between APOC3 and EPLIN in tumor tissue, but not normal mammary tissue. Furthermore, estrogen receptor–negative (ER–) and progesterone receptor–positive (PR+) tumors showed significantly increased APOC3 expression. Patients who died of breast cancer showed greater APOC3 expression, compared to disease-free individuals. APOC3 expression profile was identified as an independent prognostic factor in PR– disease, according to multivariate analysis. Patients with increased APOC3 expression experienced significant odds of developing chemotherapy resistance, independent of molecular subtype, ER status, or ERBB2 status. Further analysis showed that APOC3 was an indicator for anti-HER2 treatment sensitivity, with an AUC of 0.79.
In this retrospective analysis, researchers assessed factors associated with risk-reducing mastectomy (RRM) among patients with breast cancer and germline BRCA1/2 variants. Of 499 patients with BRCA1/2 variants, 172 (34.4%) received RRM. A total of 262 patients underwent BRCA testing before undergoing surgery, and 197 received their results prior to the procedure. Sixty-five percent of patients who knew their BRCA status before surgery underwent RRM, compared to only 18.5 percent of those who received their test results after undergoing surgery, which was a significant difference. Of the 68 patients who developed contralateral breast cancer (CBC) during follow-up, those who knew their BRCA status before surgery for CBC had a numerically, but not significantly, higher rate of RRM, compared to patients who received results after surgery (32.4% vs. 11.7%). According to multivariate analysis, timing of BRCA testing significantly affected RRM decision, as the likelihood of choosing RRM was 10.1-times higher in patients who received their results preoperatively, compared to those who were tested postoperatively. Additionally, the odds of RRM were 1.8-times higher in patients with BRCA1 mutations versus those with BRCA2 mutations. Neoadjuvant chemotherapy was also associated with increased likelihood of RRM.
In this retrospective, observational study, researchers compared the efficacy of fam-trastuzumab deruxtecan-nxki (T-DXd) and subsequent chemotherapy after chemotherapy failure in patients with human epidermal growth factor receptor 2 (HER2)–low metastatic breast cancer. Data from 347 patients were included for analysis. Most patients had Eastern Cooperative Oncology Group performance status (ECOG PS) of 1 (50.2%) or 0 (33.2%). A total of 38.3 percent of patients were on their second metastatic line of therapy, 26.5 percent were on their third line of therapy, and 35.2 percent were on their fourth or greater line of therapy. The T-DXd group consisted of 155 patients, and the chemotherapy group had 192 patients. The mortality rate was 30.3 percent in the T-DXd group at a median follow-up of 9.2 months, compared to 43.8 percent in the chemotherapy group at a median follow-up of 7.9 months. Median overall survival (OS) was not reached in the T-DXd group, compared to the 13.6 months in the chemotherapy group. The T-DXd group experienced a greater probability of survival than the chemotherapy group at six (84.1% vs. 76%), 12 (69% vs. 54.1%), and 21 months (53.9% vs. 31.2%). These findings showed that T-DXd conferred survival benefits over subsequent chemotherapy among patients with HER2-low metastatic breast cancer who failed prior chemotherapy.
Here, Inoue et al assessed the potential utility of urinary microribonucleic acids (miRNAs) as noninvasive biomarkers for detection of early breast cancer. Samples from patients aged 20 years or older who were diagnosed with Stage 0 to III primary breast cancer from October 2021 to May 2022 and had not received previous treatment were analyzed and compared to samples from 105 healthy controls. Most patients (n=170) underwent surgery as their initial treatment, and the remaining 30 patients received chemotherapy. Of 28 previously identified differentially expressed miRNAs (DEMs), 15 were upregulated and 13 were downregulated in breast cancer samples, compared to control samples. Among the patients whose first treatment was surgery, there was a significant reduction in numerous upregulated DEMs after surgery, namely, miR-22-3p, miR-374a-5p, miR-450b-5p, miR-500a-5p/500b-5p, miR-57b-5p, and miR-92b-3b. There was a significant increase in expression of the downregulated DEMs miR-125a-3p, miR-151a-5p/151b, miR-30a-3p, miR-331-3p, and miR-574-5p, whereas expression of two downregulated DEMs (miR-12136 and miR-619-5p) significantly decreased. The chemotherapy group showed similar trends in DEM expression.
Here, researchers evaluated the potential association between characteristics of calcification and ductal carcinoma in situ (DCIS) or invasive breast cancer (IBC) among individuals with benign breast disease (BBD). Sixty-five patients with BBD who developed ipsilateral DCIS (n=19) or IBC (n=46) at six months or longer post-BBD diagnosis and 244 patients with BBD who did not develop DCIS or IBC were included for analysis. There was a six-year median follow-up from BBD diagnosis to development of DCIS or IBC. Nonproliferative BBD was predominant in both cases (89%) and controls (94%). The proportion of mammographic lesions was similar between groups. Calcifications were observed in 48 percent of patients who developed DCIS/IBC, compared to 34 percent of controls; this difference trended toward significance (p=0.06). Twenty-three percent of patients who developed DCIS/IBC had fine pleomorphic calcifications, which was significantly greater than the 8.5 percent of controls with fine pleomorphic calcifications. There was no significant difference in the distribution of calcifications between groups. There was an association between calcification and development of DCIS or IBC (odds ratio [OR]: 1.7), but there was notable uncertainty. Compared to benign calcification morphology, suspicious calcification morphology (e.g., amorphous, liner, fine pleomorphic) showed an OR of 3.0.
Researchers conducted a Surveillance, Epidemiology, and End Results (SEER) database analysis to identify the causes of non-breast cancer–related mortality (NBCRM) among breast cancer survivors, as well as explore the potential link between NBCRM and high-risk disease characteristics. Data from 457,655 patients with primary breast cancer diagnosed between 2010 and 2019 were included, 4.73 percent of whom had de novo metastatic breast cancer. Median OS was 34 months and not reached for patients with metastatic and nonmetastatic disease, respectively. The metastatic breast cancer group demonstrated a significantly higher BCRM rate, compared to the nonmetastatic breast cancer group (87.76% vs. 43.44%). Regardless of presence or absence of metastatic disease, age above 50 years and age group 51 to 65 years were significantly associated with greater risk of NBCRM, compared to age of 50 years or younger. Hormone receptor–positive (HR+), HER2– disease was associated with a significantly lower risk of NBCRM, compared to triple-negative breast cancer (TNBC). Patients with Stage II or III disease experienced a greater risk of NCBRM, compared to those with Stage I disease. Among patients with nonmetastatic breast cancer, there was an association between lobular histology and reduced NBCRM risk. Receipt of radiation therapy or chemotherapy was linked to decreased risk of NBCRM and BCRM in both metastatic and nonmetastatic disease. NBCRM was attributed to cardiovascular causes in 30.76 percent of patients with nonmetastatic breast cancer and 24.78 percent of those with metastatic breast cancer. The rate of NBCRM due to subsequent malignancies was 30.24 percent in the metastatic breast cancer group and 19.62 percent in the nonmetastatic breast cancer group.
Cooke et al retrospectively analyzed data from 15 sites to compare the utility of paper screening and a digital platform on breast cancer risk stratification. Data from 2018 to June 2024 were included for analysis; paper screening forms were used from 2018 to 2021, and a digital tool was utilized from 2021 onward. In total, 168,323 mammogram appointments occurred during the paper screening era, and about one-quarter (24.6%) of individuals were eligible for genetic testing. Of the eligible individuals, 12.4 percent underwent genetic testing, six percent of whom tested positive. Twenty-two percent of individuals who received genetic testing had a lifetime risk of breast cancer of 20 percent or greater. During the digital screening era, 63,749 of 84,122 individuals (75.8%) who were invited to complete an assessment did so. A slightly greater proportion of individuals (26.3%) were eligible for genetic testing, compared to the paper screening era; 20.7 percent of eligible individuals chose to undergo genetic testing, as did 1,431 individuals who did not meet the criteria. Positive results were reported in 9.6 percent of individuals, and positive results influenced breast cancer risk management in 46.8 percent. Among individuals without a personal history of cancer, 10.6 percent were found to have a lifetime breast cancer risk of 20 percent or greater.
In this study, the relationship between chemotherapy treatment and patient-reported balance problems and falls among 1,493 survivors of breast cancer aged 65 years or older at diagnosis was explored. Patients were diagnosed between 2012 and 2013, and most patients were non-Hispanic White (83.8%). History of HR positivity and localized disease were reported in 77.1 and 76.6 percent of survivors, respectively. Adjuvant chemotherapy, most commonly taxane, was administered to 28.3 percent of patients. The incidence of self-reported severe numbness and tingling was higher in the chemotherapy group, at 12.3 percent, compared to the nonchemotherapy group, at 5.1 percent. The rate of falls within the past 12 months was similar between groups, at 32 percent for the chemotherapy group and 32.9 percent for the nonchemotherapy group. Likewise, balance problems were reported in 50.3 and 49.8 percent of patients who did and did not receive chemotherapy, respectively. Adjusted analysis showed that age and higher comorbidity scores, but not receipt of taxane, were associated with falls. However, the odds of self-reporting balance and walking issues were increased in patients who received taxane, compared to those who did not.
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