Dr. Love Reports from the 2009 ASCO Annual Meeting
June 4, 2009 The American Society of Clinical Oncology (ASCO) annual meeting took place in Orlando, Florida, May 29–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 research.
New Research Findings
Breast Cancer & PARP Inhibitors: New Treatments on the Horizon for Women with BRCA Mutations or Triple-Negative Tumors PARP, or poly (ADP-ribose) polymerase, is an enzyme that repairs damaged DNA. PARP inhibitors 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.
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 disappeared—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.
The investigators are now conducting a phase III trial in women with metastatic triple negative breast cancer. It is a multi-center randomized trial that will assess the effectiveness of the PARP inhibitor (callsed BSI-201) when combined with gemcitabine and carboplatin (GC). The trial will enroll 420 patients. A randomization process will assign half of the participants to a trial arm that will receive GC and the PARP inhibitor. The other half will receive GC alone. Importantly, the trial will have a crossover provision. This means that patients randomly assiged to receive GC alone will be able to get the PARP inhibitor if their disease progresses. You can learn more about this trial here.
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. 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).
SSRI Antidepressants and Tamoxifen 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 didn'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 antidepressant.
Ovarian Cancer: 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) it'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 woman's blood markers does not affect outcome. Either the tumor is sensitive to chemotherapy or it is not—and testing for recurrence will not change that.
Additional Findings
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!
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 "good" cancers that don't need chemotherapy.
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 don't usually save that.
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, additional studies are necessary to confirm this finding.
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.
The I-SPY Trial: UCSF'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 "good" kind and a "bad" kind of breast cancer. The women with the good kind do well, even if they don't respond all that well to the preoperative chemotherapy, whereas the women with the "bad" 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.
Educational Sessions ASCO also features educational sessions. Below are the highlights from these sessions:
Bisphosphonates This session addressed osteoporosis and its treatment, particularly as it overlaps with cancer. I was struck by the fact that we are still treating a test (bone density) and not using fractures as an end point when we discuss osteoporosis treatment with a bisphosphonate, and its effectiveness. The data show that women who take aromatase inhibitors lose bone, but that it returns when they stop the drugs. Do we really have to give them bisphosphonates to prevent the loss if it is temporary, particularly if we don't know the long-term consequences of this drug? That's the question I walked away with, and one that I wish had been addressed.
More intriguing were the findings from a study that looked at premenopausal women who were put into temporary menopause with goserelin [brand name Zoladex] and then randomized to either tamoxifen or an aromatase inhibitor followed by another randomization, to a bisphosphonate or a placebo. Apart from the fact that this is a lot of drugs for a cancer that this study showed had a 98% survival rate, the results were interesting in what they teach us about this disease. First, there was no difference between the aromatase inhibitor and tamoxifen, probably because the premenopausal women had been put into temporary menopause. Second, and more interesting, was the finding that the disease-free survival was better in either group when a bisphosphonate was added. This changes the picture, as it suggests that we should be giving bisphosphonates as cancer treatment rather than to treat the bone density test. Why would we get his result? I don't think we know. Could it be that the bisphosphonates have an effect not just on osteoclasts (the bone cells that break down bone) but the stroma (the connective tissue cells)? This is interesting and something I will continue to ponder.
Magnetic Resonance Imaging (MRI) This session reviewed the data of the use of MRI in women diagnosed with breast cancer. Bottom line: MRI can be used to monitor the size of breast cancers that are treated first with chemotherapy, IF they are the right kind of cancer. It doesn't work on all cancers, and has both false positives and negatives. But what about MRI in women who are newly diagnosed? An excellent review of the data by Dr. Houssami, concluded that MRI does not add an incremental benefit in the treatment of the disease. Part of the problem is that it finds two benign lesions for every cancer. It also leads to conversion to more extensive surgery 11% of the time. However, half of the time this is because of a false positive result. There also is no evidence that pre-operative MRI affects clinical outcome.
What about using MRI pre-operatively to find cancer in the other breast? The data show that preoperative in 9.3% of the women MRI found a suspicious lesion in the other breast, but only half of these lesions were actually cancer. MRI detects mostly "good" cancers and it is certainly not clear whether they are clinically significant.
Finally, there was a review of whether preoperative MRI leads to a lower local recurrence rate. In other words: Does MRI make the surgery better so that the woman will not have a recurrence in her breast? The answer: The recurrence rate after breast conservation is very low, and MRI does not improve it. I fully agree with the conclusion: preoperative MRI adds little to preoperative planning and does not improve the outcomes of local treatment. I am sure it is not cost effective (study not yet done) and we really have to stop routinely using this expensive imaging tool.
Sentinel Nodes Really not much new here other than the fact that you can still get lymphedema and/or numbness after a sentinel node biopsy. There is still much controversy about whether a sentinel node biopsy should be done in cases of DCIS, although it doesn't appear to add much other than side effects. There was also no consensus on whether a sentinel node biopsy should be done if there is a recurrence of the DCIS.
Vitamin D This is a complex topic, and it is not clear that low vitamin D levels are related to breast cancer risk apart from physical activity and BMI. There is also data that you can have too much vitamin D; as with everything it is a U- shaped curve with problems at both ends of the spectrum. The session confirmed my suspicion that the hype about Vitamin D is premature. The best thing we can do to prevent breast cancer is exercise, but maybe doing it outdoors will give double benefits!
Please tell us how helpful this article was for you:
Very helpful
Helpful
Not helpful
