Poor prognosis in high-risk HR+/HER2- breast cancer | MedNet

Every year, 1,200 women in the Netherlands are diagnosed with HR+/HER2 high-risk breast cancer. These patients have a poor prognosis: 1 in 4 will die of breast cancer within 10 years of diagnosis. This is evident from a retrospective study by researchers at Maastricht UMC+. “I hope that health care providers are aware of the poor progress of these women,” answered medical oncologist Dr. VCG (Vivianne) Tjan-Heijnen. She conducted the study together with a PhD student/in-training Dr.

In the study¹ Data from the Dutch Cancer Registry were used to look at women with early-stage, hormone-sensitive, HER2-negative (HR+/HER2-) breast cancer in the period 2011 to 2019 in the Netherlands. These women have a long-term risk of disease recurrence, says Geurts. “That risk remains more than 20 years after diagnosis. We know that several factors can increase the risk, such as lymph node-positive disease, larger tumors or, for example, histological grade 3.”

Study population

The study population was divided into high, moderate and low risk groups based on these factors. “In our study, high risk is defined as 4 or more positive lymph nodes, or 1 to 3 positive lymph nodes in combination with a tumor of at least 5 cm or histological grade 3,” explained Lammers. About finally, Geurts says: “That definition was also used in the international MonarchE study, on the adjunctive use of CDK4/6 inhibitors, and was accepted by several researchers.”

Compared to preview

The researchers analyzed how many patients with HR+/HER2- breast cancer have a high risk of disease recurrence, how they are treated and what their prognosis is in daily practice. Lammers: “Patients with triple-negative breast cancer are known to have a poor prognosis. We therefore compared the prognosis of patients with high-risk HR+/HER2- breast cancer with patients with triple-negative breast cancer.”

There were data from 87,455 women with HR+/HER2 breast cancer. Of these, 13% were high risk, 33% were medium risk and 50% were low risk. “That amounts to around 1,200 patients per year with a high-risk profile in the Netherlands. That’s an important group,” said Lammers. “It is important to note that the median age in this group was only 58 years. Endocrine therapy and chemotherapy were used in 38% and 7% of women at low risk, in 90% and 47% at intermediate risk, and in 94% and 73% at high risk, respectively .

According to Dutch guidelines, women with high-risk HR+/HER2-breast cancer have indications for chemotherapy, but low-risk patients do not. In practice, chemotherapy is not always given, even if there is a high risk, for example because of age or an additional illness that forces a patient to maintain the treatment. “The use of hormone therapy is a good result in 94% of high-risk patients, but the use of chemotherapy seems to be relatively low,” says Tjan.

Attractive results

Despite hormones and chemotherapy, the rate of women at high risk was still unfavorable. The 10-year survival was only 63%, the 10-year survival rate was 72%. “1 in 4 women will die of breast cancer within 10 years of diagnosis,” concluded Geurts. “We saw that this prognosis is worse in women with triple-negative breast cancer.”

These are surprising results, the researchers say. Lammers: “I think the percentage of women who die within 10 years is high. I also didn’t expect the worst progression than with triple-negative breast cancer.” Tjan also finds the numbers impressive: “I think a lot of health care providers don’t really understand this. It is known that there is a risk of metastases and the death of the patient, but in the high-risk group, relatively many patients die within 10 years median age in the high-risk group of 58 years, more than a quarter of them will not reach the age of 68. That is the age at which someone is still socially active, often involved in family life and perhaps giving past informal care for the older generation. Many people of that age are still in the middle of life. Then there is a big impact of illness and death.”

Extended hormone therapy

Regarding hormone therapy, Tjan was the principal investigator of the national DATA study, a clinical trial on the value of extended hormone therapy.² The participants received an aromatase inhibitor (anastrozole) for 3 or 6 years after 2 to 3 years of tamoxifen. Tjan: “The survival benefit in the whole group was limited, but for subgroups the difference was clinically relevant. For example, extended endocrine therapy stopped the disease from recurring within 10 years in 1 in 8 women with node-positive, estrogen and progesterone receptor-positive tumors.”

Biology of tumors

Other treatment options are being developed for women with high-risk breast cancer. But for now, Tjan believes the most important message is for healthcare providers to be aware of the poor prognosis for these women. “The number of women with breast cancer is increasingly divided into subgroups. Knowing the biology of the tumor will inform your thinking about treatment options. It is important to pay attention to the level of hormone sensitivity. I think we should use our policy in an even more different way.”

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References:

1. Lammers SW, Meegdes M, Vriens IJ, et al. Treatment and survival of patients diagnosed with high-risk HR+/HER2- breast cancer in the Netherlands: a population-based retrospective cohort study. ESMO Open. 2024; 9:103008.
2. Tjan-Heijnen VC, Lammers SW, Geurts SM, et al. Extended adjunctive aromatase inhibition after sequential endocrine therapy in postmenopausal women with breast cancer: follow-up analysis of the DATA randomized phase 3 trial. Medicine. 2023; 58: 101901.