Tag: Breast Cancer

SUMMARY: Breast cancer is the most common cancer among women in the US and about 1 in 8 women (12%) will develop invasive breast cancer during their lifetime. Approximately 290,560 new cases of breast cancer will be diagnosed in 2022 and about 43,780 individuals will die of the disease, largely due to metastatic recurrence.

The HER or erbB family of receptors consist of HER1, HER2, HER3 and HER4. Approximately 15-20% of invasive breast cancers overexpress HER2/neu oncogene, which is a negative predictor of outcomes without systemic therapy. Patients with HER2-positive metastatic breast cancer are often treated with anti-HER2 targeted therapy along with chemotherapy, irrespective of hormone receptor status, and this has resulted in significantly improved treatment outcomes. HER2-targeted therapies include HERCEPTIN® (Trastuzumab), TYKERB® (Lapatinib), PERJETA® (Pertuzumab), KADCYLA® (ado-Trastuzumab emtansine), ENHERTU® (Trastuzumab deruxtecan) and MARGENZA® (Margetuximab). Dual HER2 blockade with HERCEPTIN® and PERJETA®, given along with chemotherapy (with or without endocrine therapy), as first line treatment, in HER2-positive metastatic breast cancer patients, was shown to significantly improve Progression Free Survival (PFS) as well as Overall Survival (OS). The superior benefit with dual HER2 blockade has been attributed to differing mechanisms of action and synergistic interaction between HER2 targeted therapies. Patients progressing on Dual HER2 blockade often receive KADCYLA® which results in an Objective Response Rate (ORR) of 44% and a median PFS of 9.6 months, when administered after HERCEPTIN® and a taxane. There is however no standard treatment option for this patient population following progression on KADCYLA®.

It is estimated that close to 50% of patients with HER2-positive metastatic breast cancer develop brain metastases. Systemic HER2-targeted agents, including Tyrosine Kinase Inhibitors, as well as chemotherapy have limited antitumor activity in the brain. This is therefore an area of high unmet need. Local therapeutic interventions for brain metastases include neurosurgical resection and Stereotactic or Whole-Brain Radiation Therapy.

TUKYSA® (Tucatinib) is an oral Tyrosine Kinase Inhibitor that is highly selective for the kinase domain of HER2 with minimal inhibition of Epidermal Growth Factor Receptor. In a Phase 1b dose-escalation trial, TUKYSA® in combination with HERCEPTIN® and XELODA® (Capecitabine) showed encouraging antitumor activity in patients with HER2-positive metastatic breast cancer, including those with brain metastases.

HER2CLIMB is an international, randomized, double-blind, placebo-controlled trial in which the combination of TUKYSA® plus HERCEPTIN® and XELODA® was compared with placebo plus HERCEPTIN® and XELODA®. A total of 612 patients with unresectable locally advanced or metastatic HER2-positive breast cancer, who were previously treated with HERCEPTIN®, PERJETA® (Pertuzumab) and KADCYLA® (ado-Trastuzumab emtansine) were enrolled. Patients were randomly assigned in a 2:1 ratio to receive either TUKYSA® 300 mg orally twice daily throughout the treatment period (N=410) or placebo orally twice daily (N=201), in combination with HERCEPTIN® 6 mg/kg IV once every 21 days, following an initial loading dose of 8 mg/kg, and XELODA® 1000 mg/m2 orally twice daily on days 1 to 14 of each 21-day cycle. Stratification factors included presence or absence of brain metastases, ECOG Performance Status and geographic region. The median patient age was 54 years and patient demographic as well as disease characteristics at baseline were well balanced between the two treatment groups. In the total treatment population, 47.5% had brain metastases at baseline, 48.3% in the TUKYSA® combination group and 46% in the placebo combination group. The Primary endpoint was Progression Free Survival (PFS). Secondary end points included Overall Survival (OS), PFS among patients with brain metastases, confirmed Objective Response Rate (ORR), and safety.

In the primary analysis, at a median follow-up of 14 months, TUKYSA® added to HERCEPTIN® and XELODA®, significantly improved Overall Survival (OS) and Progression Free Survival (PFS) in patients with HER2-positive metastatic breast cancer. After the primary analysis, the protocol was amended to allow unblinding and cross-over from the placebo combination to the TUKYSA® combination. Protocol prespecified descriptive analyses of OS, PFS and safety were carried out at about 2 years from the last patient randomized. The researchers in this publication reported the final efficacy and safety outcomes after an additional 15.6 months follow up (total follow up of 29.6 months) in patients from the HER2CLIMB trial.

At a median follow up of 29.6 months, the median duration of OS was 24.7 months for the TUKYSA® combination group versus 19.2 months in the placebo combination group (HR for death=0.73; P=0.004). The estimated OS rate at 2 years was 51% in the TUKYSA® combination group and 40% in the placebo combination group. The OS benefit with the TUKYSA® combination was noted across all prespecified subgroups in the overall study population and was consistent with the primary analysis. The median duration of PFS was 7.6 months for the TUKYSA® combination group versus 4.9 months for the placebo combination group (HR for progression or death=0.57; P<0.00001), and PFS at 1 year was 29% and 14%, respectively.

Systemic treatment with TUKYSA® in combination with HERCEPTIN® and XELODA® provided consistent clinical benefit to patients with and without brain metastases. TUKYSA® combination doubled the intracranial Objective Response Rate, reduced the risk of intracranial progression or death by two-thirds in all patients with brain metastases. In this study population, the estimated 1-year intracranial PFS was 40% in the TUKYSA® group and 0% in the control group. In patients with untreated or treated and progressing (active) brain metastases, the estimated 1-year intracranial PFS was 35% in the TUKYSA® group, 0% in the control group, and in patients with treated (stable) brain metastases, was 53% in the TUKYSA® group and 0% in the control group. The TUKYSA® combination was well tolerated with a low rate of discontinuation due to toxicities. Common adverse events in the TUKYSA® group included diarrhea, Palmar-Plantar Erythrodysesthesia syndrome, nausea, vomiting and fatigue. Diarrhea and abnormal liver function tests were more common in the TUKYSA® group than in the control group.

It was concluded that with additional follow up, TUKYSA® in combination with HERCEPTIN® and XELODA® provided a clinically meaningful survival benefit, including those with brain metastases, supporting the use of this combination in patients with previously treated HER2-positive metastatic breast cancer, after progression on two HER2-targeted therapies.

Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis. Curigliano G, Mueller V, Borges V, et al. Ann Oncol. 2022;33:321-329.

SUMMARY: Breast cancer is the most common cancer among women in the US and about 1 in 8 women (12%) will develop invasive breast cancer during their lifetime. Approximately 290,560 new cases of breast cancer will be diagnosed in 2022 and about 43,780 individuals will die of the disease, largely due to metastatic recurrence. Approximately 70% of breast tumors express Estrogen Receptors and/or Progesterone Receptors and these patients are often treated with anti-estrogen therapy as first line treatment. However, resistance to hormonal therapy occurs in a majority of the patients.

Cyclin Dependent Kinases (CDK) play a very important role to facilitate orderly and controlled progression of the cell cycle. Genetic alterations in these kinases and their regulatory proteins have been implicated in various malignancies. Cyclin Dependent Kinases 4 and 6 (CDK4 and CDK6) phosphorylate RetinoBlastoma protein (RB), and initiate transition from the G1 phase to the S phase of the cell cycle. RetinoBlastoma protein has antiproliferative and tumor-suppressor activity and phosphorylation of RB protein nullifies its beneficial activities. CDK4 and CDK6 are activated in hormone receptor positive breast cancer, promoting breast cancer cell proliferation. Further, there is evidence to suggest that endocrine resistant breast cancer cell lines depend on CDK4 for cell proliferation and associated with increased expression of CDK4. The understanding of the role of Cyclin Dependent Kinases in the cell cycle, has paved the way for the development of CDK inhibitors.

KISQALI® (Ribociclib) is an orally bioavailable, selective, small-molecule inhibitor of CDK4/6, preferentially inhibiting CDK4, that blocks the phosphorylation of RetinoBlastoma protein, thereby preventing cell-cycle progression and inducing G1 phase arrest. In a phase 1b study involving postmenopausal women with ER positive, HER2-negative advanced breast cancer, KISQALI® in combination with FEMARA® (Letrozole) demonstrated an Overall Response Rate (ORR) of 46% and a Clinical Benefit Rate of 79%, in treatment-naïve patients with advanced breast cancer. This led to the design of MONALEESA-2 trial.

MONALEESA-2 trial is a randomized, double-blind, placebo-controlled, Phase III study in which 668 patients were randomly assigned in a 1:1 ratio to receive either KISQALI® plus FEMARA® or placebo plus FEMARA®. Eligible patients included post-menopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer who had received no prior therapy for advanced disease. Treatment consisted of oral KISQALI® 600 mg daily on a 3-weeks on and 1-week off schedule, in 28-day treatment cycles plus FEMARA® 2.5 mg orally daily on a continuous schedule or placebo plus FEMARA®. Patients were stratified according to the presence or absence of liver or lung metastases and treatment was continued until disease progression or unacceptable toxicity. No treatment crossover was allowed. The median age was 62 years, close to 60% of the patients had visceral metastases, and patients were stratified according to the presence or absence of liver or lung metastases. The Primary end point was Progression Free Survival (PFS) and Secondary end points included Overall Survival (OS), Overall Response Rate (ORR), Clinical Benefit Rate (Overall Response plus Stable disease lasting 24 weeks or more), Safety, and Quality of Life assessments.

In the primary and updated analyses of the MONALEESA-2 trial, PFS was significantly longer with KISQALI® plus FEMARA® than with placebo plus FEMARA® (25.3 months versus 16.0 months; HR for disease progression or death=0.57; P<0.001). The Overall Survival data were immature at the time of the primary and updated analyses. The authors have now reported the findings from the protocol-specified final analysis of Overall Survival, which is a key Secondary end point.

After a median follow up of 6.6 years, a significant Overall Survival benefit was observed with KISQALI® plus FEMARA®, compared to placebo plus FEMARA®. The median Overall Survival was 63.9 months with KISQALI® plus FEMARA® and 51.4 months with placebo plus FEMARA® (HR=0.76; two-sided P=0.008). This Overall Survival benefit was consistent across all prespecified subgroups. The median time to first subsequent chemotherapy was 50.6 months in the KISQALI® group and 38.9 months in the placebo group (HR for receipt of first chemotherapy=0.74). No new safety signals were observed.

It was concluded from the analysis of the MONALEESA-2 trial that first line therapy with KISQALI® plus FEMARA® showed a significant Overall Survival benefit as compared with placebo plus FEMARA®, in patients with HR-positive, HER2-negative advanced breast cancer, with a 24% relative reduction in the risk of death. The authors added that MONALEESA trials of KISQALI® have shown a consistent Overall Survival benefit regardless of accompanying endocrine therapy, line of therapy, or menopausal status.

Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. Hortobagyi GN, Stemmer SM, Burris HA, et al. N Engl J Med 2022; 386:942-950

SUMMARY: Breast cancer is the most common cancer among women in the US and about 1 in 8 women (12%) will develop invasive breast cancer during their lifetime. Approximately 290,560 new cases of breast cancer will be diagnosed in 2022 and about 43,780 individuals will die of the disease, largely due to metastatic recurrence.

Patients with early stage breast cancer often receive adjuvant chemotherapy to improve Overall Survival (OS), and this is even more so true for HER positive and triple negative (ER, PR and HER negative) breast cancer patients, who are at an increased risk to develop recurrent disease. Meta-analyses conducted by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) has shown a 20-25% relative risk reduction in breast cancer mortality with first-generation adjuvant chemotherapy regimens such as CMF (Cyclophosphamide/Methotrexate/Fluorouracil) and additional survival benefit with the Anthracyclines and Taxane based regimens. This benefit is dependent on the type of chemotherapy administered and chemotherapy dose intensity.

XELODA® (Capecitabine) is an oral prodrug of fluorouracil which is presently approved for the treatment of advanced breast cancer, but NOT for neoadjuvant or adjuvant treatment of early breast cancer. Meta-analysis of randomized trials has found that addition of Capecitabine to standard adjuvant chemotherapy regimens prolongs Disease Free Survival (DFS), whereas replacing a standard agent with Capecitabine did not improve DFS. Preclinical models have suggested that chemotherapy agents such as taxanes, and Cyclophosphamide increase thymidine phosphorylase concentration in the cancer cell, potentially leading to improved conversion of Capecitabine to fluorouracil within the tumor, suggesting that concomitant administration of Capecitabine with these agents improves efficacy, compared with single-agent Capecitabine. The researchers in this publication addressed the question whether addition of Capecitabine to these regimens could lead to improved survival outcomes.

The Finland Capecitabine Trial (FinXX) is a randomized, open-label, multicenter, Phase III trial that evaluated the addition of Capecitabine to an adjuvant chemotherapy regimen containing a taxane and an anthracycline for the treatment of early breast cancer. In this study, 1,500 patients with axillary node-positive or high-risk node-negative early breast cancer were randomly assigned to 6 cycles of either the Capecitabine arm- TX-CEX (N=753) or to the control group-T-CEF (N=747). TX-CEF consisted of Docetaxel 60 mg/m2 IV day 1 and Capecitabine 900 mg/m2 PO BID on days 1-15 of a 21-day cycle for 3 cycles followed by CEX consisting of Cyclophosphamide 600 mg/m2 IV Day 1, Epirubicin 75 mg/m2 IV on Day 1 and Capecitabine 900 mg/m2 PO BID on days 1-15 of a 21 day cycle for 3 cycles. T-CEF consisted of Docetaxel 80 mg/m2 IV Day 1, every 3 weeks for 3 cycles followed by CEF consisting of Cyclophosphamide 600 mg/m2 IV, Epirubicin 75 mg/m2 IV and Fluorouracil 600 mg/m2 IV, all administered on Day 1, every 3 weeks for 3 cycles. Adjuvant endocrine therapy was initiated within 2 months after completion of chemotherapy if the tumor was ER or PR-positive. Radiotherapy was given after completion of chemotherapy according to each institution’s practice. Adjuvant Trastuzumab was approved while the trial accrual was ongoing and was allowed for women with HER2-positive cancer after May 2005, and adjuvant Trastuzumab was administered to 13% patients assigned to TX-CEF and 11% patients assigned to T-CEF. The median patient age was 52.5 yrs, 76% of patients had ER-positive tumors, 19% had HER2-positive cancer, 13% had Triple Negative Breast Cancer, more than 90% had T1 or T2 tumors, and 89% were node positive. The researchers then performed a protocol-scheduled analysis of Overall Survival on the basis of approximately 15-year follow up of the patients.

At a median follow up of 15.3 years, the Overall Survival was 77.6% in the TX-CEX group and 73.3% in the T-CEF group (HR=0.81; P=0.037). Exploratory subgroup analysis suggested that patients with ER-negative disease and those with Triple Negative Breast Cancer lived longer with the addition of Capecitabine (TX-CEX regimen), than those treated with T-CEF.

It was concluded that the addition of Capecitabine to a chemotherapy regimen significantly improved Overall Survival at median follow up of 15 years in a patient population with early breast cancer, suggesting that Capecitabine may be an important addition to adjuvant chemotherapy in patients with high risk disease.

Adjuvant Capecitabine for Early Breast Cancer: 15-Year Overall Survival Results from a Randomized Trial. Joensuu H, Kellokumpu-Lehtinen P-L , Huovinen R, et al. DOI: 10.1200/JCO.21.02054 Journal of Clinical Oncology. Published online January 12, 2022.

SUMMARY: Breast cancer is the most common cancer among women in the US and about 1 in 8 women (12%) will develop invasive breast cancer during their lifetime. Approximately 290,560 new cases of breast cancer will be diagnosed in 2022 and about 43,780 individuals will die of the disease, largely due to metastatic recurrence. About 70% of breast tumors express Estrogen Receptors and/or Progesterone Receptors, and Hormone Receptor (HR)-positive/HER2-negative breast cancer is the most frequently diagnosed molecular subtype. Majority of these patients are diagnosed with early stage disease and are often cured with a combination of surgery, radiotherapy, chemotherapy, and hormone therapy. However approximately 20% of patients will experience local recurrence or distant relapse during the first 10 years of treatment. This may be more relevant for those with high risk disease, among whom the risk of recurrence is even greater during the first 2 years while on adjuvant endocrine therapy, due to primary endocrine resistance. More than 75% of the early recurrences are seen at distant sites.

Cyclin Dependent Kinases (CDKs) play a very important role to facilitate orderly and controlled progression of the cell cycle. Genetic alterations in these kinases and their regulatory proteins have been implicated in various malignancies. CDK 4 and 6 phosphorylate RetinoBlastoma protein (RB), and initiate transition from the G1 phase to the S phase of the cell cycle. RetinoBlastoma protein has antiproliferative and tumor-suppressor activity. Phosphorylation of RB protein nullifies its beneficial activities. CDK4 and CDK6 are activated in HR-positive breast cancer, promoting breast cancer cell proliferation. Further, there is evidence to suggest that endocrine resistant breast cancer cell lines depend on CDK4 for cell proliferation. The understanding of the role of CDKs in the cell cycle, has paved the way for the development of CDK inhibitors.

VERZENIO® (Abemaciclib) is an oral, selective inhibitor of CDK4 and CDK6 kinase activity, and prevents the phosphorylation and subsequent inactivation of the Rb tumor suppressor protein, thereby inducing G1 cell cycle arrest and inhibition of cell proliferation. VERZENIO® is structurally distinct from other CDK 4 and 6 inhibitors (such as Ribociclib and Palbociclib) and is 14 times more potent against Cyclin D1/CDK 4 and Cyclin D3/CDK 6, in enzymatic assays, but potentially less toxic than earlier pan-CDK inhibitors. At higher doses, only VERZENIO® causes significant cancer cell death, compared with other CDK4/6 inhibitors, suggesting that this drug may be affecting proteins, other than CDK4/6. Additionally, preclinical studies have demonstrated that VERZENIO® may have additional therapeutic benefits for a subset of tumors that are unresponsive to treatment or have grown resistant to other CDK4/6 inhibitors. It has also been shown to cross the blood-brain barrier.

VERZENIO® is presently approved by the FDA as monotherapy as well as in combination with endocrine therapy for patients with HR-positive, HER2- negative advanced breast cancer. The addition of VERZENIO® to FASLODEX® (Fulvestrant) resulted in a statistically significant improvement in Overall Survival (OS) among patients with HR-positive, HER2-negative advanced breast cancer, who had progressed on prior endocrine therapy. The goal of monarchE was to evaluate the additional benefit of adding a CDK4/6 inhibitor to endocrine therapy in the adjuvant setting, for patients with HR-positive, HER2-negative, high risk, early breast cancer.

The International monarchE trial, is an open-label, randomized, Phase III study, which included 5637 patients, who were pre- and postmenopausal, with HR-positive, HER2-negative early breast cancer, and with clinical and/or pathologic risk factors that rendered them at high risk for relapse. The researchers defined high risk as the presence of four or more positive axillary lymph nodes, or 1-3 three positive axillary lymph nodes, with either a tumor size of 5 cm or more, histologic Grade 3, or centrally tested high proliferation rate (Ki-67 of 20% or more). Following completion of primary therapy which included both adjuvant and neoadjuvant chemotherapy and radiotherapy, patients were randomly assigned (1:1) to VERZENIO® 150 mg orally twice daily for 2 years plus 5-10 years of physicians choice of endocrine therapy as clinically indicated (N=2808), or endocrine therapy alone (N=2829). The median patient age was 51 years, about 43% of the patients were premenopausal, and 95% of patients had prior chemotherapy. Approximately 60% of patients had 4 or more positive lymph nodes. The Primary endpoint was Invasive Disease Free Survival (IDFS), and Secondary end points included Distant Relapse Free Survival (DRFS), Overall Survival (OS), and Safety. The researchers provided updated results from the prespecified Primary outcome analysis, additional follow-up analysis conducted at regulatory request, as well as outcomes from prespecified subpopulations, based on Ki-67 levels.

At the time of Primary outcome analysis, with a median follow up of 19 months, 1,437 patients (25.5%) had completed the 2 year treatment period and 3,281 patients (58.2%) were in the 2 year treatment period. The combination of VERZENIO® plus endocrine therapy demonstrated superior Invasive Disease Free Survival (IDFS) compared to endocrine therapy alone, with a 29% reduction in the risk of developing invasive disease (P=0.0009; HR=0.71). The 2-year IDFS in the combination group was 92.3% and 89.3% in the endocrine therapy alone treatment group, with an absolute improvement of 3.0%. Further, there was an improvement in the 2-year distant Relapse Free Survival (DRFS) rate among patients who received the combination treatment compared with those who received endocrine therapy alone, corresponding to an absolute difference of 3.0% at 2 years (93.8% versus 90.8%, respectively; HR=0.69; P<0.001).

With 8 months of additional follow up, at a median of 27 months and with 90% of patients off treatment, the benefit with the combination of VERZENIO® plus endocrine therapy was maintained for IDFS (HR=0.70; P<0.0001) and DRFS (HR=0.69; P<0.0001), demonstrating a 30% risk reduction for IDFS and 31% risk reduction for DRFS. There was continued treatment benefit over time that extended beyond the 2-year treatment period of VERZENIO®. With more patients at risk for recurrence at 3 years, the data demonstrated absolute improvements in 3-year IDFS and DRFS rates of 5.4% and 4.2%, respectively. This treatment benefit in IDFS and DRFS was noted across prespecified subgroups. Further, the benefit with VERZENIO® was consistent, regardless of Ki-67 index. Overall Survival data was immature at the time of this analysis.

It was concluded that adjuvant VERZENIO® combined with endocrine therapy continued to demonstrate statistically significant and clinically meaningful improvement in Invasive Disease Free Survival and Distant Relapse Free Survival, among patients with HR-positive, HER2-negative, node-positive, high risk, early breast cancer, regardless of Ki-67 status.

Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Harbeck N, Rastogi P, Martin M, et al. Annals of Oncology 2021;32: 1457-1459.

SUMMARY: Breast cancer is the most common cancer among women in the US and about 1 in 8 women (12%) will develop invasive breast cancer during their lifetime. Approximately 284,200 new cases of breast cancer will be diagnosed in 2021 and about 44,130 individuals will die of the disease, largely due to metastatic recurrence.

Significant progress in breast cancer screening techniques, as well as new and novel therapies, have resulted in early cancer detection and improvement in the breast cancer 5-year survival rate in the US from 75% in the 1970s to 91% in the 2010s. Cardiovascular Disease (CVD) is the most frequent cause of noncancer-related death, and cardiotoxicities associated with cancer treatments may increase cardiovascular risk in this population of breast cancer survivors. However, few studies have in detail quantified the risks of the different clinically important cardiovascular outcomes. The authors therefore assessed the prevalence of the different clinically specific cardiovascular outcomes at breast cancer diagnosis, and their incidence after diagnosis, among survivors 65 years or older in the US, and compared this with similar women without cancer.

The researchers performed a matched cohort study using prospectively collected data from the SEER-Medicare linked claims-based database and identified all women older than 65 years of age with an incident Stage I-III breast cancer diagnosis in 2004 through 2013. Each patient with breast cancer was matched at diagnosis with 5 cancer-free female counterparts. Baseline prevalence of specific cardiovascular outcomes was measured, and the risk for individual cardiovascular outcomes during follow up was calculated, taking into consideration time since diagnosis, race/ethnicity, prior Cardiovascular Disease (CVD), and age. This study included a total of 91,473 women with breast cancer and 454,197 without breast cancer.

It was noted that women with breast cancer had lower baseline prevalence of all CVDs. Breast cancer survivors had substantially increased risks of Deep Vein Thrombosis and pericarditis, compared with cancer-free female counterparts. There was also evidence of smaller increased risks of sudden cardiac arrest, arrhythmia, heart failure, and valvular heart disease. The increased risks of arrhythmia, heart failure, pericarditis, and Deep Vein Thrombosis were most pronounced in the first year and persisted for more than 5 years after cancer diagnosis. There was evidence of a decreased risk of incident angina, myocardial infarction, revascularization, peripheral vascular disease, and stroke in breast cancer survivors, although this was not constant over time.

The CVD risk during follow up was consistently higher in African American women diagnosed with breast cancer compared with Caucasian women, regardless of whether there was an overall increased or decreased risk of outcomes during the entire follow up period, and this is consistent with racial differences in overall CVD risk in the US.

Finally, there was consistently a greater risk of all cardiovascular outcomes in those diagnosed with Stage III, Grade 3, and ER/PR-negative breast cancer, which may be a reflection of the more aggressive cancer treatment regimens used in these subtypes.

The authors concluded that there is evidence of increased risk of several cardiovascular diseases in elderly women diagnosed with breast cancer in the US, compared with similar women without cancer, with this risk persisting for several years after diagnosis. They added that these results highlight the importance of periodic cardiovascular evaluation throughout the long term follow up of women diagnosed with breast cancer.

Risk of Cardiovascular Diseases Among Older Breast Cancer Survivors in the United States: A Matched Cohort Study. Matthews AA, Hinton SP, Stanway S, et al. J Natl Compr Canc Netw 2021;19:275-284.