The American Society of Clinical Oncology (ASCO) annual meeting is taking place in Orlando, Florida, May 29 â€“ June 2, 2009. This meeting provides an opportunity for cancer researchers, doctors, and advocates to attend educational sessions as well as learn about advances in cancer science.The second day was devoted to new research findings. Here are the highlights:
Ovarian Cancer:Â Regular CA 125 monitoring is NOT beneficial in women with ovarian cancer
Researchers reported findings from a study of women who had completed their ovarian cancer treatment and were given the CA 125 blood test every three months. If the test found that their CA125 level doubled, the women were randomized to either do nothing until symptoms developed or to start chemotherapy. The study showed that the women who were treated when their CA 125 test number doubled were treated 4 months earlier, but did not have better overall outcomes than those women who were treated when symptoms developed, as both groups of women had the same survival.
This means that rather than having a regular CA 125 test (a test that makes many women very anxious) itâ€™s better just to wait to see if any symptoms of recurrence develop. The CA 125 test has been a routine part of ovarian cancer care. But this study tells us that, in fact, ovarian cancer is actually just like breast cancer, in that monitoring a womanâ€™s blood markers does not affect outcome. Â Â Either the tumor is sensitive to chemotherapy or it is notâ€”and testing for recurrence will not change that.
Breast Cancer:Â PARP Inhibitors
PARP, or poly (ADP-ribose) polymerase, is an enzyme that repairs damaged DNA. PARP inhibitorsÂ keep cancer cells from repairing their own DNA, which can make chemotherapy and radiation more effective.
Women who have a BRCA1 or BRCA2 mutation are born with a gene mutation that increases their risk of developing breast and ovarian cancer. If the BRCA1 or BRCA2 gene develops a second mutation, the cells are no longer able to perform double-strand DNA repair. (This repair is necessary to keep cells healthy, and it is the reason why these women have an increased breast cancer risk.) This means their cells can only perform single-strand repair with PARP.Â
Researchers from the UK presented data from a study in which women with metastatic breast cancer who had had at least three previous treatments with chemotherapy were given an oral PARP inhibitor; some women received a low dose, others a high dose. The study showed that 41% of the women who received the higher of the two doses responded, and in one woman the tumor completely disappearedâ€”and there were no side effects. This is an important finding, as it means that if further studies confirm these findings, will see that PARP inhibitors become widely used to treat women with BRCA mutations, in much the same way that Herceptin is used to treat women whose tumors are HER2-positive.
Even more interesting was the US study, which looked at the effectiveness of PARP inhibitors in women with triple-negative breast cancer. About 75% of women with a BRCA mutation who develop breast cancers have triple-negative tumors, but MOST triple-negative breast cancers occur in women who do NOT have a BRCA mutation. The US study was a phase II trial in which chemotherapy was given with or without a PARP inhibitor (given via IV) in women with metastatic disease. The study found that the women who received the PARP inhibitor had a 65% less likely to have a relapse and 60% less likely to die of their disease. Both findings were statistically significant. This study also found few side effects.Â The investigators now intend to conduct a phase III clinical trial.
This research finding is important because it suggests that women with triple-negative tumors with this type of cancer may have defects in the BRCA gene in their tumors, even though they do not have a BRCA mutation, and that this targeted therapy may work in a larger group of women.Â It is also significant because women with triple-negative tumors are the one group of breast cancer patients who are not currently offered a targeted therapy (aromatase inhibitor/tamoxifen for ER/PR+ tumors; Herceptin for HER2-positive tumors).
- Sentinel Node Biopsy: Studies suggest that if there are just a few isolated tumors in the axilla then the women do not need further treatment, but if there is micrometastases then you probably do.
- Post-mastectomy Radiation: Researchers reported findings from a study that suggests that women who have 1-3 positive nodes and a tumor less than 5 cm in size can benefit from radiation. But because this was a retrospective study,Â additional studies are necessary to confirm this finding.
- SSRI Antidepressants and Tamoxifen:Â Tamoxifen is metabolized in the liver into the active ingredient endoxifen. Certain drugs can block the enzyme that metabolizes tamoxifen. Studies haven shown that the SSRIs, such as paroxetine (brand name Paxil) and fluoxetine (brand name Prozac), which are used to treat depression, as well as hot flashes caused by tamoxifen, are two of the drugs that may affect tamoxifen metabolization. One study suggested that the women who were on SSRIs had an increased risk for recurrence. A second, smaller study suggested that they didnâ€™t. Bottom line: If you are on one of these SSRIs you will want to speak with your doctor about switching to a different type of anti-depressant.
- Aromatase Inhibitors and Chemobrain: Researchers presented findings from a study that showed tamoxifen had a greater impact on cognitive functioning than letrozole. Since HRT increases dementia, it may be that estrogen is not so good for the brain after all!
- Node Negative Breast Cancer: A European research group presented data from a prospective study that showed that two biomarkers, uPAH and PAI, could predict which group of node-negative women would do well even without systemic therapy. Unfortunately, we are not able to use these markers in the US because testing for them must be done on fresh frozen tissue, and we donâ€™t usually save that.
- MammaPrint & Oncotype DX: The two multiple gene tests available in this country have less data than uPAH and are only starting their large prospective studies. MammaPrint presented data from a collection of retrospective studies, and discussed MINDACT, Oncotype DX is also doing a large prospective study, called TAILORx. Interestingly, all three markers seem to detect about 40-45% of â€œgoodâ€ cancers that donâ€™t need chemotherapy.
- The I-SPY Trial: UCSFâ€™s Dr. Laura Esserman presented a report from the I-SPY Trial. This is a multicenter national trial in which women with large cancers have multiple samples and images taken before, during, and after neoadjuvant chemotherapy (this is chemotherapy given before surgery). They have found that they can use gene patterns to differentiate between a â€œgoodâ€ kind and a â€œbadâ€ kind of breast cancer.Â The women with the good kind do well, even if they donâ€™t respond all that well to the preoperative chemotherapy, whereas the women with the â€œbadâ€ more aggressive types of tumors do well only if they respond well to the preoperative chemotherapy. This is intriguing and just the first of many important findings that will come from this detailed study.Â