Too many patients with HR+ eBC are getting lost in the treatment gap

There is a significant unmet medical need in stage II and III HR+ early breast cancer (eBC)—too many patients remain at risk of recurrence despite adjuvant endocrine therapy, underscoring a gap in the treatment landscape.

Too many patients with HR+ eBC remain at risk of both early and late recurrence, even after endocrine therapy^1-4

Patients with stage II or III disease face a considerable risk of recurrence, regardless of nodal involvement. This risk persists despite adjuvant endocrine therapy and remains a significant concern for decades.

For patients with no to low nodal involvement, this risk is often underestimated. Graphic shows risk despite ET in stage II/III (N0-N1) HR+ eBC: The risk of invasive disease, including recurrence, within 3 years of diagnosis is up to 11% for N0 (no nodal involvement) and up to 13% for N1 (1-3 positive nodes). The risk of distant recurrence within 20 years is 29% for N0 and 31% for N1. 20-year rates include T1/T2 disease. Most recurrences will be to metastatic disease, for which there is currently no cure.

The 3-year and 20-year data are not from a longitudinal study.
3-year risk is based on the iDFS outcomes of patients with HR+/HER2- eBC who received endocrine therapy alone in select CDK4/6 inhibitor clinical trials.^1,2
20-year risk of distant recurrence is 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

Risk within 3 years: By stage and nodal status

Risk within 20 years: By stage and nodal status

Assessing risk is complicated—consider these factors

Table showing AJCC anatomic stage groups and other risk evaluation criteria.

Evaluating risk and prognosis is complex, and many criteria are involved⁵:

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

It is important that patients can adhere to therapy in order to effectively reduce their risk of recurrence^6-13

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:

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

Looking forward

Are your patients with stage II or III HR+/HER2- eBC falling into the treatment gap?

UNACCEPTABLE RISK OF RECURRENCE

Too many patients with stage II or III HR+ eBC remain at risk of recurrence, despite adjuvant endocrine therapy—a risk that persists across their lifetime, regardless of nodal
involvement^1-4

TOLERABILITY CHALLENGES

Nonadherence and discontinuation are associated with an increased risk of recurrence, so patients' ability to tolerate treatment is paramount^6-8

Explore a treatment option for HR+/HER2- eBC

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; BC=breast cancer; CDK=cyclin-dependent kinase; ER+=estrogen receptor-positive; ET=endocrine therapy; HER2-=human epidermal growth factor receptor 2-negative; HR+=hormone receptor-positive; iDFS=invasive disease-free survival; PR=progesterone receptor.

References
1. Mayer EL, Dueck AC, Martin M, et al. Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2021;22(2):212-222. doi:10.1016/S1470-2045(20)30642-2 2. Johnston SRD, Toi M, O'Shaughnessy J, et al. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023;24(1):77-90. doi:10.1016/S1470-2045(22)00694-5 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. 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 5. Amin MB, Edge SB, Greene FL, et al, eds; American Joint Committee on Cancer. AJCC Cancer Staging Manual. 8th ed. Springer International Publishing; 2017. 6. 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 7. 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 8. 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 9. 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 10. 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 11. 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 12. 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 13. 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

Too many patients with HR+ eBC remain at risk of both early and late recurrence, even after endocrine therapy1-4