Definition of breast cancer HR-positivity questioned
medwireNews: HER2-negative breast tumors with low hormone receptor positivity (HR low+) could be treated similarly to triple-negative tumors, suggests research from Germany that showed similar survival outcomes between the two groups.
Writing in the Annals of Oncology, Simone Schrodi (University Hospital Munich) and co-authors believe their findings demonstrate that “current definitions for HR positivity and its clinical relevance should be reconsidered.”
Schrodi and team analyzed data for 38,560 women diagnosed with early invasive breast cancer between 2004 and 2018. Of these, 2% had HR low+ expression, defined as 1–9% of cells expressing either estrogen or progesterone receptor and not more than 9% positive cells for the other receptor. A further 85% were strongly HR-positive (HR strong+; ≥10% expression) and the remaining 13% were HR-negative.
They found that patients with HR low+ tumors were significantly younger than those with HR strong+ tumors, and the HR low+ tumors were less likely to be grade 1 and more likely to have invasive histology.
Treatment types also varied among groups, with endocrine therapy given to 45% of the HR low+ group, 87% of the HR strong+ group, and 5% of the HR-negative group. Chemotherapy rates were 77%, 34%, and 79%, respectively.
In the subgroup of 33,336 individuals with HER2-negative tumors, the 10-year overall survival (OS) rate was significantly worse in those with HR low+ versus HR strong+ tumors, at 65% and 75%, respectively, and an adjusted hazard ratio for death of 0.66 in favor of the HR strong+ group.
By comparison, the rate was 66% in the HR-negative group and was not significantly different from that in the HR low+ group.
In the HER2-positive subgroup (n=5194), the 10-year OS rates were 73%, 74%, and 72% for individuals who were HR low+, HR strong+, and HR-negative, respectively, with no significant differences among the three groups in this case.
The researchers suggest that this lack of difference may be explained by “the effect of the anti-HER2 therapy [being] so strong, that prognostic factors such as HR expression have a lowered impact on outcome.”
An additional analysis, estimating the effect of endocrine therapy on patients with HR low+ tumors, revealed that this treatment had no significant survival benefit among individuals with HER2-negative/HR low+ tumors, but reduced the risk for death by a significant 27% among those with HER2-negative/HR strong+ tumors.
Schrodi et al say: “This pattern could be also shown in the HER2 positive cohort,” and therefore “irrespective of HER2 status patients with low HR positive tumors seem not to benefit from endocrine therapy.”
The authors conclude that “a prospective [randomized controlled trial] will need to replicate these findings to determine an improved treatment stratification scheme for these patient groups.”
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