Breast Cancer: Where Are We After Twenty Years?

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I recently came across a copy of a letter I wrote back in 1994, about a year after my breast cancer diagnosis, to members of a congressional committee that was considering the budget for the following year. Here is part of what I had written:

I was diagnosed with breast cancer in June 1993 at age 35, although I was considered to be at low risk for getting the disease…I read with great interest that researchers are finding some promising new leads in their study of this and other types of cancer. Discovery of the causes of and cure for cancer may not be far way, but it all depends on our continued strong commitment to providing appropriate levels of funding for basic research.

The paragraph above still represents essentially where we are today, twenty years later. That is, we continue to hear about promising new leads yet we still know little about the causes of cancer and certainly don’t have a cure.

There have been some advances in breast cancer treatment in the last twenty years, and many more women are screened each year in an effort to identify and treat breast cancer as early as possible.  But together these developments haven’t been enough to make a big difference in what really matters, the number of lives lost to breast cancer. It is fascinating to read about recent advances in cancer research and the coming advent of targeted therapies and “personalized medicine”. But these advances in understanding of the disease have not yet brought about transformational change either in the way breast cancer is treated today or in mortality from the disease.

Treatment Advances

There were several important new drug therapies for treating primary breast cancer that became available around the mid-1990s to the early 2000s. In 1994, the Food and Drug Administration (FDA) approved the chemotherapy drug Taxol (paclitaxel) for use in the adjuvant setting (after surgery for primary breast cancer). Taxol had been approved earlier for treatment of metastatic breast cancer. For HER2 positive breast cancer, the drug Herceptin (trastuzumab) has had a big impact in extending survival for many since it received FDA approval for treating breast cancer in 1998. And in 2002, for postmenopausal women with estrogen receptor positive breast cancer, the first aromatase inhibitor was approved for use in the adjuvant setting. (The drug tamoxifen, which blocks estrogen by a different mechanism, has been around since the 1970s and is still widely used in breast cancer treatment for premenopausal women.)

There have also been advances aimed at reducing “overtreatment”. The combination of breast conserving surgery with radiation became generally available in the early 1990s for most early stage breast cancer patients as an alternative to mastectomy when it was found to result in similar survival rates. Sentinel lymph node biopsy also became widely available around the same time.  The sentinel lymph node biopsy is a procedure that often eliminates the need for full lymph node dissection and reduces the risk of lymphedema. Prognostic tools such as Oncotype DX have also become available, helping doctors and patients determine when chemotherapy may not be necessary, sparing certain patients at low risk of recurrence the adverse side effects of that treatment.

It is really important to recognize though that, even with these positive developments, standard treatment for breast cancer remains essentially what it has been for decades–removal or partial removal of breasts, chemotherapy and radiation.  Also, for some of the more aggressive breast cancer sub-types, including all of those in the so-called “triple negative” category that do not overexpress the estrogen, progesterone or HER2 receptors, there are still no targeted therapies available. For no sub-type is there a verifiable cure and breast cancers can recur after many years.

For the treatment of metastatic breast cancer, there are a few more drugs available to treat the disease today than there were twenty years ago. But most of these drugs are very toxic with sometimes very severe adverse side effects, and they are not a cure.

Screening and Prevention

Much has been written about the risks and benefits of mammography. An excellent recent article that goes into depth on this subject is “Our Feel-Good War on Breast Cancer” by Peggy Orenstein in the New York Times.

There are two points on the subject of screening that I think are especially relevant as we look at where we are today compared to twenty years ago.

The first point is that today, the same as twenty years ago, we still have no screening methodology for breast cancer that can detect pre-cancerous changes when it is possible to intervene to prevent actual cancer from developing. Mammography is sometimes portrayed as preventative screening but in fact it is not able to identify pre-cancerous changes–in the way that a PAP smear does for cervical cancer or a colonoscopy does for colon cancer–at a stage when they can be removed and the development of cancer prevented.

The second point is that increased use of mammography over the last twenty years has led to a substantial increase in the numbers of women being diagnosed with a non-invasive, very early stage breast cancer known as ductal carcinoma in situ (DCIS).*  DCIS is sometimes referred to as stage zero cancer because it may or may not develop into invasive cancer. Unless it does, it is not life-threatening. However, since there is no way currently to determine whether an individual case of DCIS will or will not become invasive cancer, those diagnosed with it are generally treated with surgery and radiation, as they would be if they had early stage invasive cancer.

Also, just like twenty years ago, breast cancer prevention remains an under-studied area. We still don’t understand the initiating causes of breast cancer or how to intervene to prevent it. We still talk about causes of breast cancer almost entirely in terms of “risk factors” or associations. Inherited genetic mutations are understood to increase risk substantially for those that have them, but such inherited genetic mutations are present in less than 1% of the population and account for only about 5%-10% of breast cancer cases.*

Saving Lives

A substantial decline in deaths from breast cancer would be the result we’d hope to see from the improvements in treatments and increased screening for early breast cancer over the last twenty years. Unfortunately, that hasn’t happened.

What we have in seen instead is a moderate overall decline in mortality rates from breast cancer since the early 1990s.  As reported by the American Cancer Society (ACS), after slowly increasing between 1975 and 1990, breast cancer death rates decreased 2.2% per year between 1990 and 2007.*  However, mortality rates have not declined equally across ethnic groups. The ACS notes that a striking divergence in long-term breast cancer mortality trends between African American and white women began in the early 1980s. By 2007, death rates were 41% higher in African American than white women. It is estimated that approximately 40,000 women and men die from breast cancer annually in the United States.

Recent Advances in Basic Science and Preclinical Research

It is fascinating to read about recent advances in breast cancer research and in cancer research generally. Cancers are increasingly being understood less in terms of where in the body they originate and more in terms of the molecular characteristics that drive them. Countless potential new therapies are being studied that would target these drivers.

The hope is that these potential therapies would be both “targeted” and “personalized”. They would be targeted in the sense that they would block cellular processes that drive the cancer while sparing normal cells, thus minimizing adverse side effects. They would be “personalized” in the sense that each patient’s treatment would be based on the molecular profile of his or her cancer.

Unfortunately, for breast cancer and most other types of cancer, these next generation targeted therapies have not yet come to fruition. Translating advances in basic science to clinical application is a complex and lengthy process often ignored in news reports which frequently imply that these potential advances are reality today. Also often ignored is the extremely high cost of newer drug therapies, putting them out of the reach of many.

Looking Forward

What will it take for real progress to be made? And how can we make sure that we don’t look back twenty years from now and still say “this isn’t the kind of progress we expected to see in two decades”?

It seems that the ultimate goal is probably not so much a single cure as it is several things. First, it is having much more effective and less toxic ways to treat cancer when it does occur so that we can prevent deaths from cancer. It is making sure that everyone who needs those treatments has equal access to them. And, equally important, it is having a true understanding of the causes of the various types of cancer so we can take effective measures to prevent them.

I fervently hope that meaningful progress towards these goals can be made in the not-too-distant future. It will be the result of the hard work of the many dedicated scientists, researchers and clinicians who focus on this effort 24/7.  But for that kind of progress to occur, there will probably need to be a greater level of general awareness that results achieved to date have been more limited than many people think in terms of what really matters, saving lives.

*Source: American Cancer Society, Breast Cancer Facts & Figures 2011-2012

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