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Looking Ahead in ER+/HER2- Breast Cancer: Unpacking Long-Term Prognostic Factors
Blog Navigating ER+ HER2- Early Breast Cancer Webinar Series
Looking Ahead in ER+/HER2- Breast Cancer:
Unpacking Long-Term Prognostic Factors
Presenter: Dr. Jessica Leitsmann, Breast-Oncologist at the Breast Center of Elblandklinikum Radebeul
Abstract:
This webinar explored key insights from an international discussion on optimizing treatment for early ER-positive, HER2-negative breast cancer. Our expert emphasized the importance of integrating genomic testing (such as EndoPredict) with traditional clinical risk factors—like nodal status and tumor grade—to guide personalized treatment decisions. BRCA mutations were discussed in context, highlighting that they don’t always indicate a need for chemotherapy. The discussion also focused on the timing of genomic testing, the value of patient quality of life, and considerations around extended endocrine therapy. Overall, the discussion underscores the shift toward a more individualized, patient-centered approach to breast cancer care.
Case presentation:
Dr. Jessica Leitsmann presented a detailed case of a 45-year-old premenopausal woman with a strong family history of breast cancer, including her mother and maternal grandmother. The patient was diagnosed in August 2013 with a grade 2 invasive ductal carcinoma in the right breast, ER-positive, HER2-negative, and clinically node-negative (cT2N0M0). She had no significant comorbidities and a history of hysterectomy (without adnexal removal).
Following breast-conserving surgery with sentinel lymph node biopsy (both nodes negative), pathology confirmed a 22 mm, grade 2 tumor with hormone receptor positivity and HER2 negativity. An EndoPredict gene expression test was ordered, which indicated a low risk of distant recurrence (3% over 10 years on endocrine therapy alone), thus adjuvant chemotherapy was omitted.
Genetic testing revealed a BRCA2 mutation, and the patient subsequently underwent a laparoscopic bilateral adnexectomy (prophylactic, with benign histology). She began endocrine therapy with letrozole and completed five years of treatment, opting against extended endocrine therapy.
In March 2022, nearly nine years after the initial diagnosis, she developed DCIS in the contralateral (left) breast, confirmed by biopsy. Again, it was hormone receptor-positive. Despite her BRCA2 status, she declined prophylactic mastectomy and chose breast-conserving surgery followed by radiotherapy.
As of the presentation, the patient has had over 12 years of follow-up, remains in good health, with no evidence of recurrence or metastasis, and is not on any oncologic medications. She continues surveillance under the EIF-NP protocol for BRCA2 carriers.
BRCA mutations: not always a chemotherapy indicator
One key topic of this case presented was the presence of a BRCA2 mutation. While these are often associated with higher risk, the discussion highlighted that a BRCA-positive status alone does not automatically warrant chemotherapy. Instead, the biology of the tumor – especially when assessed using genomic tests like EndoPredict – can offer a more personalized and nuanced risk assessment. In the case presented, the patient was BRCA2-positive but had a low genomic risk score, so chemotherapy was avoided – and over a decade later, she’s still doing well.
Balancing biology, prognosis, and patient priorities in early breast cancer: insights from an international conducted survey
How do clinicians make the right treatment decisions for patients with early breast cancer, especially when traditional clinical risk factors and genomic testing seem to point in different directions? In a recent international survey, physicians from across seven countries replied to our questionnaire on how genomic testing, clinical-pathological factors, and patient preferences shape long-term treatment strategies in ER-positive, HER2-negative early breast cancer.
The power of genomic testing – at the right time
In contrast to the result of the survey in which 69% of participants requesting genomic tests after surgery only, Dr. Leitsmann emphasized that German clinical practice increasingly supports early genomic testing, even at the biopsy stage, especially in high-risk scenarios. This approach allows for better upfront decisions, such as whether to offer neoadjuvant chemotherapy. Importantly, it also gives patients clarity sooner, helping them navigate complex treatment options with confidence.
What matters most to patients? Survival – and quality of life
When patients first receive a diagnosis, the primary question they ask is simple but profound: “Am I going to survive?” Once the shock fades, other questions arise – particularly around side effects, such as hair loss, fatigue, or fertility concerns. Patients are rarely focused on whether a drug gives them two or three extra months; instead, they want to know if they can live well and live long, explained Dr. Leitsmann. Her opinion completely goes along with the ranking of answers from the survey in which we asked about the importance of factors for the initial therapy decision. The “long-term safety” followed by “as few side effects as possible” were the clear answers from the audience as well driving initial treatment considerations. This reinforces the need to look beyond clinical endpoints and integrate patient-reported outcomes and quality of life into treatment planning.
Not all risk factors are created equal
Physicians participating in the survey ranked traditional clinical parameters by their prognostic value. Nodal status came out on top, followed by tumor size and tumor grading. Interestingly, while genomic tests like EndoPredict were seen as highly valuable, they still considered just one piece of the puzzle. Many clinicians emphasized the need to interpret these scores alongside clinical data – for example, differentiating between patients with 1–3 versus 4+ positive lymph nodes.
Dr Leitsmann clearly stated that Tumor size alone isn’t everything. Small tumors can behave aggressively, while larger ones may be biologically slow-growing. Tumor grading, heterogeneity, and genomic profiles often provide a more accurate picture.
Extended endocrine therapy: who benefits?
Dr. Leitsmann explained, the decision to continue endocrine therapy beyond five years depends on the individual risk profile. Patients with intermediate genomic risk scores may benefit from extended therapy or even the addition of CDK4/6 inhibitors. However, if the predicted benefit is marginal—say, a 4% gain in a 75-year-old patient—many physicians would consider skipping chemotherapy. In contrast, a younger patient with the same risk might choose to pursue every potential advantage.
Ultimately, the patient’s voice matters. In the featured case, the woman chose to stop endocrine therapy after five years, based on her low risk and good quality of life. Twelve years later, that decision still holds up.
Takeaways: toward truly personalized cancer care
This discussion highlighted a growing shift toward patient-centric, biologically informed care in early breast cancer:
- Genomic assays like EndoPredict help personalize therapy and support long-term risk assessment – but should complement, not replace, clinical judgment.
- Nodal status remains a key predictor of distant recurrence, even in the genomic era.
- Patient quality of life, adherence, and long-term outcomes must be central in shared decision-making.
- Early integration of genomic testing (e.g., at biopsy) is increasingly valuable in planning both neoadjuvant and adjuvant strategies.
To get even more information on this topic from the exciting discussion of our experts, please watch the recording of the webinar.
