Treatment Response Foretells Events in Breast Cancer

Pam Harrison

December 06, 2018

SAN ANTONIO — Breast cancer patients who achieve a pathological complete response (pCR) to neoadjuvant therapy have a significant improvement in event-free survival (EFS) as well as overall survival (OS) compared to patients who harbor residual disease after treatment, a comprehensive, patient-level meta-analysis indicates.

"It's important to note that all of these patients received preoperative chemotherapy, so this was looking at the group in particular who had a pCR," Laura Spring, MD, instructor in medicine, Harvard Medical School, Boston, told a press briefing here during the San Antonio Breast Cancer Symposium (SABCS) 2018.

"We demonstrated that pCR was strongly associated with a higher event-free and overall survival and that the association was similar among those who received additional adjuvant cytotoxic chemotherapy after surgery versus those who did not," Spring added in a statement.

In other words, additional adjuvant chemotherapy was apparently not needed in the event of a pCR, as the extra treatment did not add efficacy.

Spring and colleagues identified 52 studies involving 27,895 patients who achieved a pCR following neoadjuvant therapy for either triple-negative breast cancer (TNBC), HER2+ breast cancer, or hormone receptor-positive/HER2 negative (HR+/HER2-) breast cancer. A pCR was defined as no signs of invasive cancer in either breast tissue or lymph nodes removed during surgery.

Study Analysis

The median follow-up for disease recurrence was 48 months while the median follow-up for OS was 49.9 months.

In the overall population, patients who achieved a pCR were 69% less likely to experience disease recurrence compared with patients left with residual disease following neoadjuvant treatment at a hazard ratio (HR) of 0.31.

At 5 years, EFS rates were 88% in pCR patients compared with 67% of patients with residual disease.

In the overall population, patients who had a pCR response to neoadjuvant chemotherapy had a 78% improvement in OS compared to those who did not have a pCR at an HR of 0.22.

Specifically, 94% of pCR achievers were alive at 5 years compared with 75% of non-pCR achievers.

The relationship between pCR and improved outcomes was strongest among those with TNBC, among whom rates of disease recurrence were 82% lower for those who achieved a pCR than they were for those who did not.

Similarly, pCR achievers with HER2+ breast cancer were 68% less likely to have disease recurrence compared with those who were left with residual disease.

The same separation between pCR achievers and nonachievers was also seen in all subgroups of patients regardless of tumor type, although a lower risk of recurrence in pCR achievers in patients with HR+/HER2- breast cancer compared with nonachievers was not significant, as Spring pointed out.

Table. EFS Rates by Subtype of Breast Cancer at 5 Years


















Results were similar between the three main subgroups when it came to OS.

The risk of recurrence also was reduced to a similar extent between patients who went on to receive adjuvant chemotherapy and those who did not.

At 5 years, patients with a pCR following neoadjuvant treatment who went on to receive adjuvant chemotherapy had an 86% EFS survival rate compared with 88% of those who did not, at an HR of 0.36 for both groups, as Spring noted.

"Results were highly significant despite inclusion of a variety of neoadjuvant therapies used, suggesting the pathway to pCR doesn't matter," Spring told delegates.

"I think [these results] support strategies where you may be able to use less cytotoxic chemotherapy where you try to identify the group who will have a pCR with de-escalation therapy, and then you spare them hopefully of getting additional cytotoxic chemotherapy," Spring concluded.

Commenting on the findings, press briefing chair Carlos Arteaga, SABCS codirector and a member of the Harold C. Simmons Comprehensive Cancer Center at the University of Texas Southwestern Medical Center in Dallas, told Medscape Medical News that since it did not matter if patients received adjuvant chemotherapy or not in terms of EFS, "it appears that the impact of chemotherapy is going to be early," he said.

Indeed, "right now for all triple-negative breast cancer patients and for just about all HER2+ breast cancer patients who have tumors greater than 2 cm, we are using neoadjuvant therapy," he elaborated.

This is supported by data that suggest using a neoadjuvant approach is at least as good as having surgery first and then adjuvant chemotherapy afterward, as he pointed out.

"The other thing is, if you can shrink the tumor, you can get a lot of women to breast conservation surgery," Arteaga added.

"So for patients who achieve pCR, they are going to do well, and that's good news," he suggested.

Based on the current meta-analysis, the overall pCR rate achieved across the 52 studies was 21.1%, but it varied depending on the tumor subtype involved, as Spring noted.

For example, for cohorts of HER2+ breast cancer as well as those with TNBC, "the overall pCR rate was more in the mid-30s," she explained.

On the other hand, when the tumor was HR+/HER2-, the pCR rate was under 10%.

Spring reports that she has served as a consultant or on the advisory board for Novartis and has received institutional research funding from Tesaro. Arteaga has disclosed no relevant financial relationships.

SABCS 2018: Abstract GS2-03. Presented December 4, 2018.


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