Delays exceeding 90 days between breast cancer diagnosis and surgery, or between phases of treatment, have been reported to be associated with less favorable outcomes. Tumors of newly diagnosed women normally have been growing for several years before being detected. Therefore, in order for delays to make a difference in prognosis, diagnosis and treatment must cause changes that result in accelerated metastasis. This raises the question as to whether women with more aggressive types of breast cancer are more vulnerable to the potentially harmful effects of delays in treatment. Now a new study has reported that a delay of more than 90 days in starting chemotherapy after surgery is associated with worse survival, especially among women with triple negative (ER-/PR-/HER2-) disease.
Why delays matter
Delay after biopsy
Delays between a diagnosis of breast cancer (using needle biopsy) and breast surgery or neoadjuvant chemotherapy (chemotherapy designed to shrink the tumor before surgery) have been linked to reduced survival. One study published this month reported that each 30-day delay (compared to surgery during the first 30 days after diagnosis) was associated with a 10% reduction in survival for stage I and stage II (but not stage III) disease. The study included 115,790 U.S. invasive breast cancer patients over 18.
One possible explanation for worse outcomes associated with delays before treatment is the potential for needle tract seeding. Needle tract seeding occurs when breast cancer cells are deposited along the path of the biopsy needle as it is withdrawn from the breast.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 has any influence on survival have been reassuring. It is not clear whether needle biopsies involving taking multiple tissue samples can cause the degree of damage to tumor tissue that could promote metastasis (as described in the next section).
Radiotherapy appears to be an effective method for destroying any breast cancer cells dispersed in the breast by a needle biopsy. However, the needle tract must be part of the radiation field. It is also preferable that any subsequent lumpectomy (or more extensive breast conserving surgery) remove all of the tissue immediately surrounding the biopsy needle path.
Delay after surgery to remove tumor
Surgical removal of the primary tumor is a necessary and effective treatment for breast cancer. However, surgery induces changes in the expression of genes implicated in metastasis—tumor removal is followed by accelerated growth of locally recurrent tumors and metastases. One study using a mouse model of breast cancer reported that metastases in the mice that underwent tumor removal demonstrated heightened proliferation. Surgery significantly increased the expression of genes involved in cancer cell adhesion, invasion, and angiogenesis in the mice. Recent evidence suggests that use of opiates during surgery might also increase the likelihood of metastasis. These factors could help explain why delays appear to reduce the benefit of further treatment. Therefore, it is important that surgery for all but the smallest tumors be followed in a timely manner by radiation and/or systemic treatment in order to eradicate any remaining cancer cells.
Latest research links delays over 90 days to worse outcomes
The study referenced at the beginning of this news story was designed to identify the reasons for delays in chemotherapy and to investigate the relationship between time to chemotherapy and outcome according to breast cancer subtype. The authors used data from the California Cancer Registry concerning 24,843 women with stage I to III invasive breast cancer. The women were diagnosed between 2005 and 2010 at a median age of 53 years, and treated with chemotherapy after undergoing surgery to remove the tumor. Time to chemotherapy was defined as the number of days between surgery and the first round of chemotherapy. The median was time to chemotherapy was 46 days. Time to chemotherapy exceeding 90 days was classified as a delay.
The following factors were found to be associated with delays in initiation of chemotherapy: low socioeconomic status; Hispanic or African-American ethnicity; insurance other than private health insurance; and breast reconstruction.
Compared to women who started chemotherapy within 30 days after surgery, women who started chemotherapy on days 31 through 90 were not found to have worse outcomes. However, when the delay stretched past 90 days, the women had a 27% higher risk of breast cancer-specific death. When the data was analyzed according to breast cancer subtype, women with triple negative disease were found to have a 53% higher risk of breast cancer-specific death after a 90+ day delay in beginning chemotherapy. The authors conclude that delaying initiation of adjuvant chemotherapy for more than 90 days is associated with poorer prognosis. Delays are particularly detrimental for those with triple negative breast cancer. Such delays are often associated with sociodemographic factors. All breast cancer patients should be provided with timely care.
Please see our article on triple negative prognosis for more information.