Adjuvant chemotherapy offers limited benefit for invasive lobular carcinoma
SAN ANTONIO — Adjuvant chemoendocrine therapy did not extend survival compared with endocrine monotherapy for patients with invasive lobular carcinoma, according to retrospective study results presented at San Antonio Breast Cancer Symposium.
Only one-third of patients in the cohort underwent genomic testing. However, most of the tested cases were characterized as low risk to intermediate risk.
The findings suggest a limited role for chemotherapy in the treatment of invasive lobular carcinoma, researcher Megan Kruse, MD, medical oncologist with Cleveland Clinic Taussig Cancer Institute, told Healio.
“However, we need to keep in mind that this is a retrospective analysis, so there is certainly selection bias for which patients received chemotherapy,” Kruse said. “That being said, the propensity score matching analysis helps to show that when clinical/pathologic features are matched between endocrine therapy and chemoendocrine therapy groups, the outcomes were still similar.
“How we apply these data in clinic is unclear,” she added. “In the absence of prospective, randomized data, I think it is worrisome to make a blanket statement that no [patients with invasive lobular carcinoma] benefit from chemotherapy. Ultimately, we would like to have a biomarker ... that helps to determine which patients would benefit from chemotherapy; however, that does not yet exist.”
Invasive lobular carcinoma — which accounts for approximately 15% of breast cancer cases — is the second most common histological type of invasive disease, behind only invasive ductal carcinoma.
Most invasive lobular carcinomas are hormone receptor positive, and they generally are considered to be less chemosensitive than invasive ductal carcinoma.
“When we see patients in the clinic with invasive lobular carcinoma, we will often recommend chemotherapy based on clinical characteristics, such as tumor size, lymph node involvement and patient age. However, many providers feel that chemotherapy does not add much to the long-term cancer control outcomes for such patients,” Kruse told Healio. “We wanted to look at patients with invasive lobular carcinoma treated at Cleveland Clinic to see if giving chemotherapy helped to improve outcomes.”
Kruse and colleagues used Taussig Cancer Institute’s tumor registry to identify patients (mean age, 61.9 years) with nonmetastatic invasive lobular carcinoma treated at the institution between January 2004 and December 2017.
Researchers compared survival outcomes between those treated with adjuvant endocrine therapy and those who received chemoendocrine therapy, and they compared outcomes between age and pathological stage propensity score-matched treatment groups.
Investigators also assessed utilization of genomic testing with the 21-gene recurrence score (Oncotype Dx, Genomic Health) — a common gene expression profile test — and assessed whether results correlated with outcomes and chemotherapy benefit, as has been observed among patients with hormone receptor-positive, HER2-negative breast cancer.
The analysis included 638 patients, most of whom had ER-positive disease (99.1%) and PR-positive disease (82.6%).
Approximately two-thirds (63.6%; n = 406) of patients received endocrine monotherapy and one-third (36.4%; n = 232) received chemoendocrine therapy.
Patients who received chemoendocrine therapy were significantly younger (mean age, 56.3 years vs. 65 years) and more likely to be premenopausal (40.1% vs. 14.6%). However, they also were significantly more likely to have poorer prognostic features, including disease grade (grade 2, 69% vs. 55.9%), pathological stage (stage III, 38.9% vs. 2.1%) and Oncotype Dx recurrence score (18, 72.4% vs. 36.2%).
Median follow-up for survival was 4 years (interquartile range, 2-6.4).
Results showed a lower rate of 5-year RFS in the chemoendocrine therapy group (81.9% vs. 96.5%). However, when adjusted for age and clinical prognostic features, researchers reported no significant difference between the chemoendocrine therapy and endocrine monotherapy groups with regard to recurrence risk (adjusted HR = 0.83; 95% CI, 0.36-1.92) or risk for death (adjusted HR = 0.68; 95% CI, 0.31-1.5).
Slightly more than one-third (35%, n = 222) of patients received Oncotype Dx recurrence scores. Nearly all scores placed patients at low risk (59%) or intermediate risk (39%) for recurrence. Only 2% of patients received scores that suggested high risk for recurrence.
Recurrence scores did not appear associated with recurrence or death.
When researchers compared age- and pathological stage-matched groups based on treatment regimen, they reported no significant difference in 5-year RFS (97.4% vs. 90.4%) or 5-year OS (94.3% vs. 89.4%) between those who received chemoendocrine therapy and those who received endocrine monotherapy.
“I was surprised that only 35% of this study population had Oncotype Dx testing done when 85% of patients would have potentially been candidates for testing using the inclusion criteria from the TAILORx studies,” Kruse told Healio. “I suspect that this reflects provider assumptions about invasive lobular carcinoma, as many of the cancers in this study — approximately 40% — were low grade.”
The fact that 40% of included patients were aged older than 65 years also may have been a factor, as they may not have wanted chemotherapy or been good candidates for it. In those cases, testing would not have been sent as it would not influence the treatment plan, Kruse said.
“These would be interesting questions to look at in the future,” she said.
Kruse and colleagues, along with other collaborators, are investigating the optimal treatment — in both the curative-intent and metastatic settings — for patients with invasive lobular carcinoma.
Because of the relatively low prevalence of invasive lobular carcinoma, most of these efforts will need to occur at the multi-institutional or national levels, she said.
“I personally feel that the preoperative or neoadjuvant treatment setting is a great place to compare treatment strategies for patients with invasive lobular carcinoma and am hoping to develop trials in this area,” Kruse said. – by Mark Leiser
Thomas M, et al. Abstract 1760. Presented at: San Antonio Breast Cancer Symposium; Dec. 10-14, 2019; San Antonio.
Disclosure: Kruse reports an advisory board role with Novartis Oncology. Please see the abstract for all other authors’ relevant financial disclosures.