 |
 |
 |
 |
 |
 |
|
||||||||||||||
| Tracks 1-14 | ||||||||||||||||||||||||||||||
|
Select Excerpts from the Interview
Track 2
DR LOVE: Can you review where we are currently with adjuvant
endocrine therapy?
DR MACKEY: Tamoxifen used to be our only option for hormonal therapy for
postmenopausal women. Although tamoxifen is a good drug — in that it shows
a significant survival advantage, prevents recurrences and prevents contralateral
breast cancer — it still has some Achilles’ heels. One of the major problems is
that prolonged tamoxifen use can trigger endometrial cancer and blood clots.
The nice aspect of the aromatase inhibitor story is that anastrozole, letrozole and exemestane have been shown in several trials in postmenopausal women to improve the chances of remaining free of breast cancer when used instead of tamoxifen, when used to replace part of the five-year course of tamoxifen and even when used after five years of tamoxifen. For almost any patient you see in your practice who has had breast cancer within the past five years, if she’s postmenopausal and has ER-positive or PR-positive disease, there may be a role for an aromatase inhibitor.
The data are maturing over time, and 10 adjuvant aromatase inhibitor trials have reported in one fashion or another. Probably the most exciting element is that several groups have taken the results from these trials, put them all into a hat, shaken them up in a meta-analysis and demonstrated that not only is disease-free survival improved by the aromatase inhibitors, but convincing evidence is also emerging that overall survival is improved (Mauri 2006).
Tracks 4-5
DR LOVE: Where are we in terms of determining the optimal duration to
administer aromatase inhibitor therapy?
DR MACKEY: The jury is still out on that issue. The ATAC (Howell 2004)
and BIG 1-98 (BIG 1-98 2005; Coates 2007) trials show that if you start
postmenopausal women on either anastrozole or letrozole immediately after
recovery from surgery, they do quite well and better than with tamoxifen.
However, we also have trials that suggest if patients are halfway through their five-year course of tamoxifen, switching them to any one of the three aromatase inhibitors will provide a disease-free advantage. Even after five years of tamoxifen, switching to an aromatase inhibitor will improve the disease-free survival. The remaining question is whether 15 years is better than 10 years of hormonal therapy.
DR LOVE: What about the issue of delayed endocrine therapy?
DR MACKEY: That is still somewhat of an open question. It appears that
the aromatase inhibitors can reduce the chance of breast cancer recurrence,
whether used immediately after diagnosis, after two or three years or after
five years. There are also data suggesting that even beyond five years after
diagnosis you can start a patient on an aromatase inhibitor and see a benefit.
Track 7
DR LOVE: Can you discuss gynecologic issues with aromatase inhibitors
compared to tamoxifen (4.1)?
DR MACKEY: Tamoxifen can trigger endometrial cancer. Particularly in the
postmenopausal population, the longer a patient is receiving it, the more
likely she is to experience endometrial abnormalities. Tamoxifen can also trigger vaginal discharges and thickening of the endometrium — changes that
lead the gynecologist to become concerned and perform D&Cs to rule out
endometrial carcinoma.
In fact, the ATAC trial showed that, with long enough follow-up, about five percent of women on tamoxifen ended up having a hysterectomy (Howell 2004). Women who received anastrozole for five years had a rate of endometrial cancer of 0.2 percent. They had fewer problems with vaginal discharge, and the hysterectomy rate was about a quarter of what was seen on the tamoxifen arm.
Tracks 10, 14
DR LOVE: Where are we right now in terms of quality control for
estrogen receptor and HER2 testing?
DR MACKEY: Modern management of early-stage breast cancer hinges on two
predictive assays, the estrogen receptor status and the HER2 oncoprotein or
HER2 oncogene status. There have been a number of rude awakenings in the
last decade, such as the realization that the testing we conducted in the past
was largely inadequate and relatively difficult to standardize.
DR LOVE: Do you believe that the Oncotype DX assay will replace the
technology we’re using right now to measure ER and HER2?
DR MACKEY: It’s possible, although technically it is more difficult to do the
Oncotype DX because you’re actually taking several sections of the tumor from
the block, grinding them up and extracting the RNA, then doing a quantitative
RT-PCR assay.
The nice aspect of conducting the assay in that complex fashion is that you have internal controls. You also know whether you have a bad sample or a good sample, and it removes some of the variability associated with tissue fixation differences and some of the biological problems that immunohistochemistry faces. Although these are more expensive and more complex, I believe nucleic acid-based technologies like Oncotype DX or FISH testing in a multiplex assessment of a patient’s tumor will outperform our “old war horses” — immunohistochemical assays.
Track 13
DR LOVE: In what subset of patients with node-negative, ER-positive
tumors is Oncotype DX most useful?
DR MACKEY: When you’re considering women with node-negative, ER-positive
tumors, the first thing to evaluate is tumor size. If they have big
tumors — two or three centimeters — and they have Stage II disease, they
warrant a discussion of chemotherapy. In that case, I wouldn’t send these
tumors for Oncotype DX testing.
The question in my mind involves women who have T1 lesions (which are two centimeters or smaller), particularly the ones that aren’t high grade. This is the subset of ER-positive breast cancer cases in which the Oncotype DX would return information that could inform your chemotherapy decision.
| Table of Contents | Top of Page |
Editor:
Neil Love, MD
Interviews
J Michael Dixon, MD
- Select publications
Maura N Dickler, MD
- Select publications
William C Wood, MD
- Select publications
John Mackey, MD
- Select publications
 |
 |
 |
 |
 |
