Cancers Can Vanish Without Treatment, but How?

[Hopeful]

http://www.nytimes.com/2009/10/27/health/27canc.html

Hopeful

[gdpawel]

The New York Times reports a paper in The Journal of the American Medical Association noted that data from more than two decades of screening for breast and prostate cancer call that view into question.

Besides finding tumors that would be lethal if left untreated, screening appears to be finding many small tumors that would not be a problem if they were left alone, undiscovered by screening. They were destined to stop growing on their own or shrink, or even, at least in the case of some breast cancers, disappear.

When women in four Norwegian countries began regular mammography every two years, breast cancer rates increased significantly, and this suggests that the mammography may have be detecting cancers that might have spontaneously regressed, according to an article released on November 24, 2008 in the Archives of Internal Medicine, one of the JAMA/Archives journals.

The start of regular screening through mammography in Europe was associated in increased incidence of breast cancer -- this is a relatively normal consequence of any new screening program. However, the authors note, "if all of these newly detected cancers were destined to progress and become clinically evident as women age, a fall in incidence among older women should soon follow." They continue, noting that this has not occurred: "The fact that this decrease is not evident raises the question: What is the natural history of these additional screen-detected cancers?"

To investigate the etiology of these newly identified cancers, Per-Henrik Zahl, M.D., Ph.D., of the Norwegian Institute of Public Health, Oslo, and colleagues observed breast cancer rates in women who were invited to participate in three rounds of screening mammograms between 1996 and 2001 in the Norwegian Breast Cancer Screening Program. A total of 119,472 women between the ages of 50 and 64 participated.

The rates in these women were compared to a control group in the same age range in 1992 who would have been invited for screening, if the program had existed in that year. National registries were used to track cancer rates. At the end of six years, these control women were invited to participate in a one-time screen for cancer prevalence.

Breast cancer rates were higher in the screened population than in the control group -- this was expected, as they were being checked more regularly. However, when the control group was screened, the total number of cancer diagnoses in the control population was lower than those in the screened group. "Even after prevalence screening in controls, however, the cumulative incidence of invasive breast cancer remained 22 percent higher in the screened group," write the authors.Over the course of the six years, 1,909 of the screened women in every 100,000 had breast cancer. In contrast, 1,564 of every 100,000 women in the control group had breast cancer. This was also true for every stratified age.

The authors give a potential explanation for these absent cancers: "Because the cumulative incidence among controls never reached that of the screened group, it appears that some breast cancers detected by repeated mammographic screening would not persist to be detectable by a single mammogram at the end of six years," they say. "This raises the possibility that the natural course of some screen-detected invasive breast cancers is to spontaneously regress."

They continue: "Although many clinicians may be skeptical of the idea, the excess incidence associated with repeated mammography demands that spontaneous regression be considered carefully." They add that this is not an unlikely scenario: "Spontaneous regression of invasive breast cancer has been reported, with a recent literature review identifying 32 reported cases. This is a relatively small number given such a common disease. However, as some observers have pointed out, the fact that documented observations are rare does not mean that regression rarely occurs. It may instead reflect the fact that these cancers are rarely allowed to follow their natural course."

Their findings cannot make a statement about mammograms' ability to prevent breast cancer deaths, they say. "Instead, our findings simply provide new insight on what is arguably the major harm associated with mammographic screening, namely, the detection and treatment of cancers that would otherwise regress."

Robert M. Kaplan, Ph.D., of the University of California, Los Angeles, and Franz Porzsolt, M.D., Ph.D., of Clincal Economics University of Ulm, Germany, contributed an accompanying editorial that notes that lack of knowledge which still persists about the natural history of breast cancer. "Despite the appeal of early detection of breast cancer, uncertainty about the value of mammography continues," they write. "In this issue of the Archives, Zahl et al use a clever study design in an attempt to estimate the value of screening."

"Perhaps the most important concern raised by the study by Zahl et al is that it highlights how surprisingly little we know about what happens to untreated patients with breast cancer," they continue. "In addition to not knowing the natural history of breast cancer for younger women, we also know very little about the natural history for older women. We know from autopsy studies that a significant number of women die without knowing that they had breast cancer (including ductal carcinoma in situ). The observation of a historical trend toward improved survival does not necessarily support the benefit of treatment."

"If the spontaneous remission hypothesis is credible, it should cause a major re-evaluation in the approach to breast cancer research and treatment. Certainly it is worthy of further evaluation," they finally conclude.

The Natural History of Invasive Breast Cancers Detected by Screening Mammography
Per-Henrik Zahl, MD, PhD; Jan Mæhlen, MD, PhD; H. Gilbert Welch, MD, MPH Arch Intern Med. 2008;168(21):2311-2316.

The Natural History of Breast Cancer
Robert M. Kaplan, PhD; Franz Porzsolt, MD, PhD Arch Intern Med. 2008;168(21):2302-2303.

Dr. Robert M. Kaplan, chairman of the department of health services at the School of Public Health at the University of California, Los Angeles, who with his colleague, Dr. Franz Porzsolt, an oncologist at the University of Ulm, wrote an editorial that accompanied the study, were persuaded by the analysis, and feel the implications are potentially enormous.

Dr. Barnett Kramer, director of the Office of Disease Prevention at the National Institutes of Health, had a similar reaction. People who are familiar with the broad range of behaviors of a variety of cancer, know spontaneous regression is possible, but what is shocking is that it can occur so frequently.

And Donald A. Berry, chairman of the department of biostatistics at M. D. Anderson Cancer Center said the study increased his worries about screening tests that find cancers earlier and earlier. Unless there is some understanding of the natural history of cancers that are found, the result can easily be more and more treatment of cancers that would not cause harm if left untreated.

Dr. Berry felt that it's possible that we all have cells that are cancerous and that grow a bit before being dumped by the body. Screening tests may pick up minute tumors that would not progress and might even go away if left alone (pseudodisease). Patients will be alarmed and exposed, perhaps needlessly, to the risks of chemotherapy, surgery and radiation.

Spontaneous remissions in cancer suggests that the body can heal itself. It seems like most apparently occur in just a few types of malignancies: malignant melanoma, renal cell cancer, low-grade non-Hodgkin's lymphoma, chronic lymphocytic leukaemia and neuroblastoma in children. However, spontaneous remissions do occur in vastly different other types of cancers.

The very existence of spontaneous remissions represents a threat to some in the cancer industry. But such anomalies can pave the way to a better understanding of the causes of cancer which can then lead to rational therapies. Historical observations of spontaneous remissions of breast cancer after the onset of menopause lead to approaches of hormonal treatment which is a mainstay of adjuvant and palliative therapy in breast cancer.

Regardless, spontaneous remissions represent an important clue as to how the body can defend itself against cancer. Researchers should think "outside the box" at this important phenomenon rather than see it as a threat to their conventional thinking and appreciate the insight it may provide to rational approaches to cancer treatment.

For some common cancers, it is not clear that early detection and treatment actually prolong patients' lives. Early detection may just mean patients spend a longer time knowing they have cancer, and yet die at the same time they would have died anyway if the tumor had been diagnosed later. A decision to forgo cancer screening can be a reasonable option.

Literature Citation: Arch Intern Med. 2008;168(21):2300, 2302-2303, 2311-2316.

[Jean]

After reading this I have two main thoughts.
While this article says MAY have cancers that shrink and just go away...but....

I do not feel comfortable with this article on two levels.
1. Just maybe since screening the reason for a higher level of breast cancers is due to the fact that mammograms are being performed. dah...am I missing a point?

2. I have to consider those who have HER2 bc ...those would be suspect NOT to just shrink and go away on their own....along with Infamatory Breast Cancer.

While many women are still dying of this dreaded disease....the numbers are lower than 20 years ago.
hmmm....I think we must acknowledge that breast exams have aided women more than hurt them. Early detection does saves lives.

I still believe like any other parts of our body we need to have regular check ups just like having our teeth checked on a regular basis. As we age, it is much more vital to have blood tests, pap smears, eyes exams and other routine exams. Gosh why omit any part of the body. I think way too much picking is happening regarding mammograms.....to me it is no different than other body part that we want to ensure is healthy.

Okay, my 2 cents worth.
Jean

[Hopeful]

I am one of the people who had a spontaneous regression of cervical in situ cancer, which was discovered only AFTER I underwent a cervical conization, a very painful experience that left me with a permanently compromised cervix. This only happened because I went for my regular screening, which was scheduled for 3 months after I had had a clean pap smear as part of a pre-operative work up. The entire experience has definitely colored my opinion of cancer screening and treatment, and had a profound effect on how I approached my BC diagnosis and tx.

I agree that we cannot just "count on" any kind of cancer just going away until we have testing that can show us which ones will (and which ones won't) progress. I am, though, very leery of the standard agressive overtreatment we use on all cancers. Sometimes, less is more.

Hopeful

[gdpawel]

Hopeful

I agree too that we cannot just count on any kind of cancer just going away until we have testing that can show us which ones will and which ones won't progress.

Have you heard of any of the assays of genetic expression in tumor tissue as a technique to determine prognosis in patients with breast cancer?

The genetic analysis of Oncotype DX predicts which women will have a greater chance of breast cancer recurrence. The test looks at 21 genes that influence the behavior of breast cancer cells.

MammaPrint looks at the expression of 70 genes linked to breast cancer with an accuracy level of 96.7% as determined by a study published in the New England Journal of Medicine.

Mammostrat is validated utilizing five immunohistochemical biomarkers to classify patients into high, moderate, or low-risk categories for disease recurrence.

Until these tests, it had been difficult to pinpoint which women would benefit most from chemotherapy, and those which wouldn't. These tests enable the oncologist and breast cancer surgeon to more accurately determine who should be treated and who should not be treated with chemotherapy, but they cannot predict "chemo response."

Patients in the high-risk group, who would benefit from chemotherapy, could be pre-tested with a cell-based functional bio-marker to see what treatments have the best opportunity of being successful, and offers a better chance of tumor response resulting in survival, while those in the lower-risk groups can be spared the unnecessary toxicity, particularly associated with ineffective treatment.

There should be due consideration to looking at the advantage of molecular and cellular assay tests.

[Hopeful]

gdpawel,

I had the Oncotype test and regret having done so, because all it did for me was raise anxiety levels. I have done extensive reading and research since my dx, and I have reservations as to how sensitive that test is for Her2+ patients - the formula for risk calculation that the test uses weighs that particular gene very heavily. As research into Her2+ bc continues, studies show that not all Her2+ bc is equal, but the current version of Oncotype treats them that way. Thus far, all of the validation studies have been done in retrospective cases. I will be most interested in seeing the results of the TailorX trial, limited to Her2- patients, to see how the results stack up against the validation studies.

The fact that researchers are developing tests of any type to try and distinguish characteristics of individual cancers that will better direct treatment is a very positive development. Like every new techonology, it requires refinement, which will come the more they are used.

Hopeful

[gdpawel]

Hopeful

The Oncotype DX test looks at 21 genes that influence the behavior of breast cancer cells. The MammaPrint has some superiority over the Oncotype DX because it looks at the expression of 70 genes (as opposed to only 21) linked to breast cancer with an accuracy level of 96.7% as determined by a study published in the NEJM.

While these tests have been shown to be superior over conventional assessment of risk of future metastatic disease, one gets more accurate information when using intact RNA isolated from "fresh" tissue than from using degraded RNA, which is present in paraffin-fixed tissues.

The NCI has a huge lab working on microarrays to look for patterns of mRNA and protein expression which are predictive of chemotherapy response. They spent two years trying to find patterns which correlated using the NCI's various established ovarian cell-lines.

They thought they had something, but when they started to apply them to "fresh" tumor specimens, none of the results in the cell-lines was applicable to the "fresh" tumors. Everything they worked out in the cell-lines was not worth anything and they had to start over from square one.

However, the limitations and non-applicability of the NCI efforts failed to realize that the way to identify informative gene expression patterns is to have a "gold standard" and the (cell-death) cell culture assays are by far the most powerful, efficient, useful "gold standard" to have, adding the potential value of the assays to individual cancer therapy.

In regards to "accuracy" of a test. The CellSearch System (like PET imaging) is a test that can be done after therapy to monitor results. A friend went to a symposium devoted entirely to the CellSearch technology. He came out of it thinking it's not of value in "selecting" therapy and it is really not all that accurate.

The cut off is 5 tumor cells. Less than 5 means that things are going well. More than 5 means that things are going poorly. But you can see that the difference between 4 and 6 is not all that great. It could perhaps, be useful as an adjunct to traditional methods for following tumor response, such as xrays, blood tests, MRIs, history, physicial exam, etc.