Undue delays between breast cancer treatment steps have been reported to be associated with less favorable outcomes, although not all studies are in agreement. A delay can potentially occur simply as a result of scheduling problems each time a women transitions between different treatment providers. However, delays appear to be more common for older breast cancer patients, as well as those who are African American or economically disadvantaged. Women with more aggressive types of breast cancer (e.g., triple negative (ER-/PR-/HER2-), HER2+, or inflammatory breast cancer (IBC)) are more vulnerable to the potentially adverse effects of treatment delays.
Delays between a diagnosis of breast cancer (using needle biopsy) and neoadjuvant chemotherapy (chemotherapy designed to shrink a tumor before surgery) have been linked to worse outcomes. Now a new study has reported that delays in neoadjuvant chemotherapy of more than 60 days after breast cancer diagnosis are associated with increased risk of death.
Why delay in neoadjuvant chemotherapy matters
Tumors of newly diagnosed women normally have been growing for several years before being detected. In cases of very indolent disease, very small tumors could potentially remain untreated for extended periods of time without affecting prognosis. Therefore, in order for a delay in starting neoadjuvant chemotherapy for early stage breast cancer to make a difference, the process of diagnosis must cause important changes. In fact, physically disturbing a tumor appears to increase its metastatic potential. For example, surgery has been shown to induce modifications in the expression of genes implicated in metastasis. These changes result in increased cancer cell proliferation and motility (ability to move), thereby allowing such cells to escape into circulation. It is possible that needle biopsies involving taking multiple tissue samples may cause the degree of damage to tumor tissue that could promote metastasis.
Another possible explanation for worse outcomes associated with treatment delays is the potential for needle tract seeding. Needle tract seeding occurs when breast cancer cells are deposited along the path of a biopsy needle as it is withdrawn from the breast. Evidence suggests that such seeding does occur 20% to 50% of the time. However, most breast cancer cells moved by biopsy needles do not survive — studies that have examined the question as to whether such seeding influences survival have been reassuring. However, even if unlikely, the potential for needle tract seeding is another reason that treatment should occur in a timely manner after biopsy.
Latest research links delay to increased risk of death
The study referenced above was designed to investigate whether time between diagnosis and beginning of neoadjuvant chemotherapy is associated with survival. Women selected to undergo neoadjuvant chemotherapy normally have breast cancer with high-risk features, a fact that the authors took into account in performing the analysis. The study included 5,137 patients treated for invasive primary breast cancer (stage I–III) with neoadjuvant chemotherapy at MD Anderson Cancer Center between 1995 and 2015. The women were divided into three groups according to days from breast cancer diagnosis to neoadjuvant chemotherapy: 0 to 30, 31 to 60, and at least 61 days. Participants were followed for a median of 6.9 years.
The five-year overall survival was 87% for those who started neoadjuvant chemotherapy within 30 days, 85% for 31 to 60 days, and 83% for more than 60 days after diagnosis. Further analysis showed that the association between delay in neoadjuvant chemotherapy and increased risk of death was statistically significant for patients with stage I or stage II breast cancer (but not stage III), and among patients with HER2+ tumors. The authors conclude that a delay in neoadjuvant chemotherapy of more than 61 days after breast cancer diagnosis is associated with increased risk of death. Early initiation of neoadjuvant chemotherapy should be a priority, according to the authors.
Please see our treatment delays tag for more information.