An update from Prof. Sabine Linn and her research group at the Antoni van Leeuwenhoek on what the research supported by A Sister’s Hope has achieved in recent years. Liever in het Nederlands? Lees Behandeling op maat bij borstkanker.
Less Chemotherapy When Possible
For an aggressive type of breast cancer called triple-negative breast cancer, there is now strong evidence that some patients may not need chemotherapy before or after surgery. This appears to be possible when a tumor is surrounded by a very large number of immune cells.
This approach may be suitable if:
- The tumor is 2 cm (about 0.8 inches) or smaller.
- The lymph nodes in the armpit are not affected.
- Cancer cells are not found in lymphatic vessels or blood vessels.
To confirm that this strategy can be safely used in everyday clinical practice, three large studies are currently being conducted in Europe and the United States.
If these studies confirm the findings, it is expected that 10-20% fewer patients with Stage I triple-negative breast cancer will need chemotherapy in the future. This could improve quality of life by avoiding both the short-term side effects of chemotherapy and long-term risks such as heart failure.
Targeted Treatment for High-Risk Breast Cancer
A specific type of Stage III HER2-negative breast cancer can have a feature called homologous recombination deficiency (HRD). This type is seen most often in younger women, typically around their forties.
Stage III means that the cancer is advanced in the breast and nearby tissues but has not yet spread to distant parts of the body.
This form of breast cancer carries a high risk of returning within two to four years. If it does return, survival is often limited.
Researchers from the Antoni van Leeuwenhoek Hospital, together with all Dutch academic hospitals, the Medical Spectrum Twente, and a center in Marseille, France, conducted the SUBITO study. They investigated whether a known weakness of these cancer cells could be used against them. Because these cancer cells have difficulty repairing DNA damage, researchers wanted to determine the most effective treatment strategy.
They compared:
- A short but very intensive treatment with high-dose chemotherapy followed by a stem cell transplant.
- A less intensive chemotherapy schedule combined with longer-term targeted treatment.
What did they find?
After four years, survival rates were similar in both groups.
The results suggest that the longer, less intensive treatment is the preferred option, because it is just as effective while causing fewer side effects.
An important part of this treatment is a medication called olaparib, taken for one year. Unfortunately, olaparib is currently not yet available for this indication in the Netherlands, although it is available in other European countries.
Other Important Findings
Immune Cells and Triple-Negative Breast Cancer
A high number of immune cells around a Stage I triple-negative breast cancer is generally a favorable sign. However, this benefit disappears if cancer cells have already spread into lymphatic vessels or blood vessels.
Hormone Therapy After Chemotherapy
For women diagnosed between the ages of 45 and 55 with hormone receptor-positive, HER2-negative breast cancer, who also receive chemotherapy before or after surgery, treatment with an aromatase inhibitor appears to be more effective than treatment with tamoxifen.
However, regular blood tests are important to ensure that the ovaries remain inactive. Aromatase inhibitors do not work properly if the ovaries are still producing hormones and menstrual cycles are continuing.
Timing of Trastuzumab Treatment
For HER2-positive Stage I-III breast cancer, trastuzumab is usually given at the same time as chemotherapy. Research suggests that, for many patients, receiving chemotherapy first and trastuzumab afterwards may be just as effective.
Limits of the PREDICT Tool
PREDICT is an online tool used to estimate:
- A patient's prognosis.
- The potential benefits of chemotherapy.
- The benefits of trastuzumab.
- The benefits of hormone therapy.
Research shows that PREDICT is not sufficiently reliable for women diagnosed before the age of 40.
BRCA1-Related Findings
Changes in the BRCA1 gene are relatively common in women under 40 with triple-negative breast cancer.
For Stage I triple-negative breast cancer, prognosis improves as the number of immune cells around the tumor increases. This effect is especially strong when cancer cells show a change called BRCA1 promoter methylation.
For every 10% increase in immune cells:
- The relative risk of death decreases by about 16%.
- In tumors with BRCA1 promoter methylation, the reduction is approximately 31%.
In addition, patients with Stage I triple-negative breast cancer and BRCA1 promoter methylation appear to have a very low risk of developing a second breast cancer.
Lobular Breast Cancer in Young Women
In women younger than 40 with hormone receptor-positive, HER2-negative invasive lobular breast cancer measuring up to 5 cm and without affected lymph nodes:
- Tumor grade does not appear to predict outcome.
- Prognosis is less favorable when cancer cells have spread into lymphatic or blood vessels.
- Prognosis is also less favorable when multiple tumors are present in the breast.
Researchers also found that patients whose tumors are both estrogen receptor-positive and progesterone receptor-positive, and have a low or intermediate tumor grade (Grade 1 or 2), may have a higher risk of developing distant metastases over 15 years if they have invasive lobular breast cancer compared with the more common type of breast cancer known as NST (No Special Type) carcinoma.
Summary
These studies move breast cancer treatment closer to personalized care. By identifying which patients need less treatment and which patients benefit from specific targeted therapies, doctors can improve outcomes while reducing unnecessary side effects and maintaining quality of life.
References
Publications supported by A Sister’s Hope (2021 to 2026).
- de Jong VMT, Wang Y, Ter Hoeve ND, et al. Prognostic Value of Stromal Tumor-Infiltrating Lymphocytes in Young, Node-Negative, Triple-Negative Breast Cancer Patients Who Did Not Receive (neo)Adjuvant Systemic Therapy. J Clin Oncol 2022; 40(21): 2361-74.
- Leon-Ferre RA, Jonas SF, Salgado R, et al. Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer. JAMA 2024; 331(13): 1135-44.
- de Boo LW, Jozwiak K, Ter Hoeve ND, et al. Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naive patients with triple-negative breast cancer. ESMO Open 2024; 9(3): 102923.
- Seefat RL, Vliek SB, de Jong VMT, et al. Targeting homologous recombination deficiency with intensified chemotherapy versus standard chemotherapy followed by olaparib in stage III breast cancer (SUBITO): an open-label, randomised, controlled, phase 3 trial. Lancet Oncol 2026; 27(7): 795-807.
- Dackus G, Jozwiak K, Sonke GS, et al. Adjuvant Aromatase Inhibitors or Tamoxifen Following Chemotherapy for Perimenopausal Breast Cancer Patients. J Natl Cancer Inst 2021; 113(11): 1506-14.
- Dackus G, Jozwiak K, van der Wall E, et al. Concurrent versus sequential use of trastuzumab and chemotherapy in early HER2+ breast cancer. Breast Cancer Res Treat 2021; 185(3): 817-30.
- Wang Y, Broeks A, Giardiello D, et al. External validation and clinical utility assessment of PREDICT breast cancer prognostic model in young, systemic treatment-naive women with node-negative breast cancer. Eur J Cancer 2023; 195: 113401.
- Wang Y, Dackus G, Rosenberg EH, et al. Long-term outcomes of young, node-negative, chemotherapy-naive, triple-negative breast cancer patients according to BRCA1 status. BMC Med 2024; 22(1): 9.
- Voorthuis RAB, Opdam M, Ter Hoeve ND, et al. Invasive lobular breast cancer in young patients without adjuvant systemic treatment: 15-year survival outcomes. Breast Cancer Res Treat 2026; 218(3).