Ralph W. Moss, Ph.D.

The use of adjuvant chemotherapy after surgery for breast cancer is often presented as one of oncology's great success stories. The early use of chemotherapy is based on the assumption that such treatment will eliminate any remaining tumor cells (called micro-metastases), thereby decreasing the chance that cancer will return, and improving the odds of survival. Systemic adjuvant treatment has therefore become strongly recommended for many women with the disease.

In the past 10 years there has been a shift towards the use of drugs called anthracyclines in the adjuvant setting. The most prominent of these – and now a standard of care – is Adriamycin (doxorubicin).

A 1998 meta-analysis, called the EBCTCG study, analyzed the results that had previously been found in 47 clinical trials using various combinations of chemotherapy vs. no chemotherapy. It concluded there was a significant reduction in the death rate among patients receiving any combination of chemotherapy drugs.

For instance, in women who were younger than 50 years at randomization, combination chemotherapy improved 10-year survival from 71 to 78 percent for those with node-negative disease (an absolute benefit of 7 percent), and from 42 to 53 percent for those with node-positive disease (an absolute benefit of 11 percent). For women 50 to 69 years of age at randomization, there was a gain in 10-year survival from 67 to 69 percent for those with node-negative disease (an absolute gain of 2 percent) and from 46 to 49 percent for those with node-positive disease (an absolute gain of 3 percent).

Why did this meta-analysis tip the scales towards Adriamycin, a drug that (according to Jerome Groopman, MD, of Harvard Medical School) oncologists nicknamed "the red death," due to its cranberry color and its toxicity?

Included in this study there were 11 trials in which women received anthracyclines in preference to the once predominant regimen known as CMF. At five years, the overall survival was 72 percent among the patients receiving anthracyline-based chemotherapy vs. 69 percent among those receiving CMF, an advantage of 3 percent. Small though this difference was, it was considered sufficient basis for the recommendation that Adriamycin be adopted as the treatment of choice.

Today, the two basic competing types of adjuvant chemotherapy for breast cancer are still a CMF-type chemotherapy regimen or an anthracycline-based regimen using either Adriamycin or a similar drug, epirubicin. These two regimens differ in their adverse effect profiles. Anthracycline-based regimens may cause hair loss, vomiting, and mouth sores (mucositis) and also have a significant long-term risk of damaging the heart muscle. In contrast, CMF is more likely to cause nausea and premature menopause, although it too is capable of causing heart damage.

Anthracyclines are included in a number of different regimens:

AC chemotherapy: Adriamycin and cyclophosphamide

CAF (also known as FAC): cyclophosphamide, Adriamycin and 5-FU

CEF (also known as FEC): cyclophosphamide, epirubicin and 5-FU

These combinations in turn may be used with one of the drugs known as taxanes – either Taxol or Taxotere – both of which are derived from the Pacific yew tree. There are of course vigorous debates over the relative merits of these treatments. But suffice it to say that the US National Cancer Institute has concluded that there is "a slight advantage for the anthracycline regimens in both premenopausal and postmenopausal patients." Because of this, many women with stage II breast cancer or even stage I cancer now receive anthracyclines, particularly Adriamycin, as part of their adjuvant treatment.

Bazell Report

It was in this context that I read with interest a recent news report by Robert Bazell, NBC's chief science and health correspondent. Bear in mind that Bazell has written a book on the development of the breast cancer drug Herceptin and is particularly well versed on topics relating to this disease. In the past he has stood almost alone in the mainstream media for being willing to criticize the National Cancer Institute.

See, for example, my earlier newsletter:

Writing for, Bazell reports on a private session that was held at the meeting of the American Society of Clinical Oncology (ASCO) in Chicago earlier this month. At this closed session, a select group of attendees was addressed by Dr. Dennis Slamon, chief of oncology at UCLA. Dr. Slamon revealed that his current research indicates that anthracyclines such as Adriamycin almost certainly provide no benefit whatever to 92 percent of breast cancer patients. Only 8 percent of all women with breast cancer – those who over-express a specific gene called Topoll-2 – stand to benefit from anthracycline-based chemotherapy, since these drugs work by directly targeting Topoll-2.

Meanwhile, Adriamycin and related drugs are well known to be cardiotoxic, causing permanent heart damage in a significant proportion of patients. They are also associated with an increased risk of second cancers, particularly leukemia.

The fact that over 90 percent of women who are given anthracycline-based chemotherapy can expect to derive absolutely no benefit – and potentially considerable harm – from this treatment is a momentous admission. It is all the more remarkable coming from a source as unimpeachable as Dr. Slamon, whose research was pivotal to the development of another ‘targeted' breast cancer drug, Herceptin.

"It seems apparent that we are treating patients who don't need the drug to get at that group who have a huge benefit," Slamon told Bazell. "And now we need to direct our therapy and target it more specifically." Unfortunately, at present there is no commercial test for Topoll-2, although according to Dr. Slamon, development of a test is apparently nearing completion.

It cannot come a moment too soon. The fact that tens of thousands of women are routinely being given chemotherapy that can only possibly benefit 8 out of every 100, and that may harm considerably more than it helps, is shocking.

Although Dr. Slamon's work has not yet been peer-reviewed or published in any medical journal, Bazell considered it newsworthy enough to publish at the MSNBC Web site. Aside from the Annie Appleseed Project (, almost no one on the Internet has seemingly noticed this important report.

I made a similar point a dozen years ago in my book, Questioning Chemotherapy. Analyzing the case of some women with node-negative disease, I wrote that toxic chemotherapy was being given to 100 node-negative women in order to benefit just 3. "To achieve that goal for 5,040 women, 64,960 other women have to be treated with toxic drugs," I wrote. "They cannot and will not derive any benefit from this treatment" (p. 91, emphasis in original). After the book came out, I actually rented a display booth at ASCO, in order to familiarize oncologists with this sobering fact. Overall, I met with deafening silence. Oncologists seemed uninterested in any facts that might lead them to diminish the increasing use of chemotherapy.

While the specific numbers have changed somewhat since 1995, it is still true that large numbers of women have to be treated with toxic drugs in order for a few to benefit. If Dr. Slamon has truly figured out how to test women for their sensitivity to anthracyclines then this would be a great thing, since it will spare a huge number of women from having to take these potentially heart-damaging and leukemia-inducing drugs.

If that happens, this will represent a further turn towards individualizing cancer treatment, so that only those who are really likely to benefit from a drug need to receive it. This will be excellent news for the 100,000 or so women each year who are now given anthracyclines with little or no chance of benefiting from them, but with a considerable risk of harm.

Ralph W. Moss, Ph.D.


The Jerome Groopman quote can be found in his book, How Doctors Think, as well as at:

You can read Robert Bazell's report at:

My book, Questioning Chemotherapy, is available in bookstores or from Amazon:,_amazon/102-1261320-7650503?ie=UTF8&tag=cancerdecisio-20&link%5Fcode=

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