More than 1 in 3 patients with ER+ eBC are lost in the treatment gap

Too many patients with stage II or III ER+ early breast cancer (eBC) remain at risk of distant recurrence despite current treatment options, underscoring a significant gap.

WATCH: An expert discusses this unmet medical need

The risk of recurrence for many patients with ER+ eBC is unacceptable^1,2

In eBC, 42% of all patients are diagnosed with stage II or stage III disease—and many of them remain at risk of distant recurrence despite adjuvant endocrine therapy.^1,2

Even after 5 years of ET, the risk of distant recurrence remains high. 1 in 3 patients with stage II disease and 1 in 2 patients with stage III disease will experience distant recurrence within 20 years. Analysis included patients with T1/T2 disease and <10 involved nodes.

42% estimate based on data from Surveillance, Epidemiology, and End Results (SEER) registries.¹
Risk of recurrence statistics derived from a meta-analysis of 78 randomized trials in the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) database of 74,194 women with ER+ breast cancer who had 5 years of scheduled endocrine therapy.³

Assessing risk is complicated—consider these factors

Table showing AJCC anatomic stage group criteria for stage II and stage III early breast cancer.

In addition to TNM criteria, other considerations for determining risk and prognosis include⁴:

Histologic grade
ER, PR, and HER2 status
Genomic profile scores (eg, OncotypeDx^®)
Circulating tumor cells and disseminated tumor cells
Ki-67
Age
Menopausal status
Comorbidities

Stage II and III disease include a range of tumor sizes and nodal involvement, which may impact the risk of distant recurrence²

A Kaplan-Meier curve displaying the rates of distant recurrence over 20 years for patients with stage II and stage III ER+ eBC who had 5 years of endocrine therapy. At 20 years: T1N1 is 27%; T2N0 is 29%; T2N1 is 37%; T1N2 is 46%; T2N2 is 57%.

From a meta-analysis of 78 randomized trials in the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) database of 74,194 women with ER+ breast cancer who had 5 years of scheduled endocrine therapy. Patients with T1 or T2 disease and fewer than 10 involved nodes were included in the analysis. Rates shown represent risk at 20 years.³

In HR+/HER2- eBC, recently approved adjuvant treatments are limited to patients at the highest risk of recurrence^5,6

Adjuvant endocrine therapy has been the standard of care for patients with HR+ eBC for over 3 decades. Though targeted adjuvant treatments have recently been introduced, their limited indications highlight a gap in the treatment landscape.^1,5-9

These recently approved targeted treatments are each only approved for use in <15% of patients with eBC, leaving the majority lost in the treatment gap. Percentage represents the proportion of eligible patients out of all stages of eBC.

Calculation based on targeted therapy approval for stage II or III node-positive HR+/HER2- disease and prevalence of BRCA1 and BRCA2 germline mutations in ER+ breast cancer.^1,5,6,9

Patients need treatments that can help them live their fullest lives^10-17

It is important that patients can adhere to therapy in order to effectively reduce their risk of recurrence. Many patients will need to be on therapy for years, so their ability to tolerate treatment is paramount. Symptomatic adverse reactions contribute to poor tolerability and are commonly associated with^10-17:

Patients' inability to live their fullest lives Nonadherence to therapy Higher rates of discontinuation

Expert perspective

BELOW: Dr Aixa Soyano Muller discusses the treatment gap in HR+/HER2- eBC

Proof 278624 eBC DSA Campaign Refresh ME Video 4.23

Looking forward

Too many patients with HR+/HER2- stage II or III eBC have fallen into the treatment gap

UNACCEPTABLE RISK OF RECURRENCE

More than 1 in 3 patients with stage II and III ER+ eBC are at risk of distant recurrence, despite receiving adjuvant endocrine therapy²

LIMITED TREATMENT OPTIONS

Recently approved targeted treatments are each only approved for use in <15% of patients with eBC—leaving many lost in the treatment gap^1,5,6,9

TOLERABILITY CHALLENGES

Nonadherence and discontinuation are associated with an increased risk of recurrence. Treatments with improved tolerability are needed^10-12

COMMITTED TO CLOSING THE GAP For more than 35 years, Novartis has been tackling breast cancer by focusing on the unmet medical needs of our patients and customers

Definitions and references

AJCC=American Joint Committee on Cancer; ER+=estrogen receptor-positive; ET=endrocrine therapy; HER2-=human epidermal growth factor receptor 2-negative; HR+=hormone receptor-positive; PR=progesterone receptor.

References:
1. Howlader N, Altekruse SF, Li CI, et al. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. 2014;106(5):dju055. doi:10.1093/jnci/dju055 2. Pan H, Gray R, Braybrooke J, et al; EBCTCG. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med. 2017;377(19)(suppl):1836-1846. doi:10.1056/NEJMoa1701830 3. Pan H, Gray R, Braybrooke J, et al; EBCTCG. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med. 2017;377(19):1836-1846. doi:10.1056/NEJMoa1701830 4. Amin MB, Edge SB, Greene FL, et al, eds; American Joint Committee on Cancer. AJCC Cancer Staging Manual. 8th ed. Springer International Publishing; 2017. 5. Lynparza. Prescribing information. AstraZeneca Pharmaceuticals LP. 6. Verzenio. Prescribing information. Eli Lilly and Company. 7. Huppert LA, Gumusay O, Idossa D, Rugo HS. Systemic therapy for hormone receptor-positive/human epidermal growth factor receptor 2-negative early stage and metastatic breast cancer. CA Cancer J Clin. 2023;73(5):480-515. doi:10.3322/caac.21777 8. Elliott MJ, Cescon DW. Development of novel agents for the treatment of early estrogen receptor positive breast cancer. Breast. 2022;62(suppl 1):S34-S42. doi:10.1016/j.breast.2021.11.007 9. Hu C, Hart SN, Gnanaolivu R, et al. A population-based study of genes previously implicated in breast cancer. N Engl J Med. 2021;384(5):440-451. doi:10.1056/NEJMoa2005936 10. Pistilli B, Lohrisch C, Sheade J, Fleming GF. Personalizing adjuvant endocrine therapy for early-stage hormone receptor–positive breast cancer. Am Soc Clin Oncol Educ Book. 2022;42:60-72. doi:10.1200/EDBK_350358 11. Collin LJ, Cronin-Fenton DP, Ahern TP, et al. Early discontinuation of endocrine therapy and recurrence of breast cancer among premenopausal women. Clin Cancer Res. 2021;27(5):1421-1428. doi:10.1158/1078-0432.CCR-20-3974 12. Ejlertsen B, Jensen M-B, Mouridsen HT; Danish Breast Cancer Cooperative Group. Excess mortality in postmenopausal high-risk women who only receive adjuvant endocrine therapy for estrogen receptor positive breast cancer. Acta Oncol. 2014;53(2):174-185. doi:10.3109/0284186X.2013.850738 13. Ahmed N, Vengalasetti Y, Haslam A, Prasad V. Association of adjuvant or metastatic setting with discontinuation of cancer drugs in clinical trials. JAMA Netw Open. 2022;5(5):e2212327. doi:10.1001/jamanetworkopen.2022.12327 14. Smith KL, Verma N, Blackford AL, et al. Association of treatment-emergent symptoms identified by patient-reported outcomes with adjuvant endocrine therapy discontinuation. NPJ Breast Cancer. 2022;8(1):53. doi:10.1038/s41523-022-00414-0 15. Brett J, Fenlon D, Boulton M, et al. Factors associated with intentional and unintentional non-adherence to adjuvant endocrine therapy following breast cancer. Eur J Cancer Care (Engl). 2018;27(1). doi:10.1111/ecc.12601 16. Fontein DBY, Nortier JWR, Liefers GJ, et al. High non-compliance in the use of letrozole after 2.5 years of extended adjuvant endocrine therapy. Results from the IDEAL randomized trial. Eur J Surg Oncol. 2012;38(2):110-117. doi:10.1016/j.ejso.2011.11.010 17. Hershman DL, Kushi LH, Shao T, et al. Early discontinuation and nonadherence to adjuvant hormonal therapy in a cohort of 8,769 early-stage breast cancer patients. J Clin Oncol. 2010;28(27):4120-4128. doi:10.1200/JCO.2009.25.9655

The risk of recurrence for many patients with ER+ eBC is unacceptable1,2