Modified Drug Combination Decreases Disease Recurrence in High Risk, HER2 Negative Breast Cancer

Breast Cancer, Breast Cancer Awareness Ribbon, Pink.

Providing expert commentary on findings from a large study conducted by German investigators demonstrating that a modified drug combination may lead to a decreased chance of disease recurrence for women with high risk, HER2 negative breast cancer, Masey Ross, MD., medical director of the Integrative Health Program and breast medical oncologist at Massey, and Charles Geyer, Jr., MD., associate director for clinical research, Harrigan, Haw, Luck Families Chair in Cancer Research and breast medical oncologist at Massey, agree that nab-paclitaxel, a chemotherapy drug that is also known by its brand name, Abraxane® (Celgene), may be a new standard of care in neoadjuvant therapy of high-risk early breast cancer.

The editorial, co-authored by Ross ad Geyer, was published in the Journal of Clinical Oncology.

 Masey Ross, MD, MS1 and Charles E. Geyer Jr, MD, FACP

Masey Ross, MD, MS, and Charles E. Geyer Jr, MD, FACP. Photo Courtesy: VCU Massey Cancer Center, Richmond, Virginia.

Ross and Geyer shed an optimistic light on the potential for a shift in the treatment protocol for an important subset of patients with early breast cancer.

Current standard of care
Neoadjuvant chemotherapy is the current standard of care for most women with lymph node positive or high risk, lymph node negative breast cancer.

The regimen typically includes the use of the solvent-based drug paclitaxel sold under the brand name Taxol® (Bristol-Myers Squibb Company) among others, which often contributes to allergic reactions and nerve damage in many patients.

Research reported by the German Breast Group (GBG) in 2016 had demonstrated that the substitution of the albumin-based drug nab-paclitaxel instead of paclitaxel.

Complete pathologic response
Paclitaxel prior to surgery improved chances for a complete pathologic response at the time of surgery in patients with triple negative breast cancer, but not with other disease subtypes. A complete pathologic response refers to the elimination of all invasive cancer in the breast and lymph nodes.

Nab-paclitaxel was initially approved as a treatment for metastatic breast cancer in 2005.

New findings
New findings published by the German Breast Group revealed that the groups of patients who received nab-paclitaxel instead of the standard paclitaxel before surgery experienced improved long-term outcomes, meaning more of them were alive and disease-free following their surgery. This was found to be the case for women with triple negative, hormone receptor positive and HER2 positive breast cancers.

These findings challenge a prevailing viewpoint in oncology by suggesting that drugs that aren’t effective in increasing the percentage of complete pathologic responses could still result in better long-term outcomes.

“The study is interesting because it makes us rethink whether drugs administered prior to surgery that do not improve chances of having a complete response should be discarded under the assumption that they will not decrease a patient’s risk of recurrence after surgery,” noted Ross, who is also an assistant professor of internal medicine at the VCU School of Medicine.

While the GBG findings indicate that nab-paclitaxel was more effective than standard paclitaxel for breast cancer patients across the board, Geyer and Ross believe that these study results could be particularly important for one breast cancer subtype over the other types.

“In our opinion, this information is most applicable in women with hormone receptor positive, HER2 negative breast cancer,” said Geyer, also a member of the Developmental Therapeutics research program at Massey and a professor of internal medicine at the VCU School of Medicine.

“We feel it may not be particularly relevant for patients with HER2 positive breast cancer because substantial improvements in HER2 directed therapies co-administered with chemotherapy in this subset have occurred since the German study finished accruing patients. The improvements seen with nab-paclitaxel came at a cost of increased rates of neuropathy, and alternative approaches available for patients with HER2 positive breast cancer are associated with less neuropathy.”

Nerve damage
Neuropathy, a debilitating form of nerve damage, may prevent HER-2 positive breast cancer patients from being able to tolerate subsequent administration of highly effective drugs such as T-DM1 that are significantly beneficial for women who did not have a complete pathologic response at the time of surgery.

Triple-negative breast cancer
For triple negative breast cancer patients, some oncologists incorporate the use of a chemotherapy agent called carboplatin, which has been shown to improve chances for a complete response when administered before surgery.

The study conducted by the GBG did not factor in the use of carboplatin; therefore, it remains unclear how nab-paclitaxel will interact with it for this patient group.

“We suggest that physicians who do not incorporate carboplatin into treatment for women with triple negative breast cancer should consider nab-paclitaxel over standard paclitaxel,” Ross concluded.

Reference
[1] Ross M, Geyer CE Jr. Nab-Paclitaxel: A New Standard of Care in Neoadjuvant Therapy of High-Risk Early Breast Cancer? J Clin Oncol. 2019 Jul 15:JCO1900877. doi: 10.1200/JCO.19.00877. [Pubmed][Article]