Causes of Cancer

Ionizing Radiation (Fluoroscopy/ Mammography/Medical X-Rays)

Proven Causes of Breast Cancer

Our current estimate is that about 75% of the current annual incidence of breast cancer in the U.S. is being caused by earlier ionizing radiation, primarily from medical sources.
Mammography — radiation-induced breast cancer.
John W. Gofman, M.D., Ph.D., Committee for Nuclear Responsibility, P.O. Box 421993, San Francisco, CA 94142, in Preventing Breast Cancer: The Story of a Major, Proven, Preventable Cause of This Disease.

Introductory notes by HCN

The following excerpts from Dr. John W. Gofman's above-quoted book provide incontrovertible proof that mammography and ionizing radiation received on the chest lead to an increased breast cancer risk.

In fact, other authors have arrived at similar conclusions. A study looking into the link of breast cancer to exposure to multiple diagnostic X-rays found that women exposed to an average of 25 X-rays before the age of 20 had a 70 % higher breast cancer risk than the general female population.^[1]

Another study reports that "Young women with Hodgkin's disease treated with high levels of radiation to the chest are much more likely to develop secondary breast cancer than women on less aggressive radiation regimes...

The study found that the breast cancer risk was eight times higher among women exposed to the highest levels of radiation than women who were given the smallest doses, where those women were treated before age 30.

The risk persisted years after treatment, with the high-dose group still more than twice as likely to develop breast cancer than the low-dose group 25 years later, according to the study in the Journal of the American Medical Association.

Similarly, "'The findings by researchers at the National Cancer Institute in Bethesda, Maryland, confirm the thinking that women with Hodgkin's disease (cancer of the lymphatic system) should be given only as much radiation as is necessary to eliminate the primary cancer [a stance not shared by Healing Cancer Naturally].

Survival rates for Hodgkin's disease (HD) have increased significantly in the last 50 years — the five-year survival rate in the United States is now 85 percent, according to the Institute.

But the improvement in treatments has been accompanied by an increased risk of secondary cancers, with breast cancer the most likely form to strike women. ... Increased rates of breast cancer have been generally attributed to chest irradiation for HD, consistent with the known sensitivity of the breast to ionizing radiation at young ages.

The evidence "supports the notion that 'lower is better' as long as the radiation dose used augments the cure rate for HD,' wrote Joachim Yahalom, an expert in radiation oncology with New York's Memorial Sloan-Kettering Cancer Center in an accompanying editorial. ...

Researchers based their findings on a study of 3817 women diagnosed with HD at age 30 or younger between 1965 and 1994, 105 of whom went on to develop breast cancer. – (Sapa-AFP)"

Ionizing Radiation as a Preventable Breast Cancer Cause

excerpted from the book Preventing Breast Cancer: The Story of a Major, Proven, Preventable Cause of This Disease, (1996), by John W. Gofman, M.D., Ph.D. "This book uncovers the major cause of the recent breast cancer incidence in the USA.

The author shows that past exposure to ionizing radiation --- primarily medical x-rays --- is responsible for about 75 percent of the breast cancer problem in the United States. The good news: Since the radiation dosage given today by medical procedures can be significantly reduced without interfering with a single useful procedure, numerous future cases of breast cancer can be prevented.

The author recommends specific actions to start breast cancer prevention now, not ten years from now."

CHAPTER 1: Our Conclusion: A Large Share of Breast Cancers Need Not Occur

Part 1. The Bottom Line

We begin this book with our bottom line, because we think the advice of Sara Jeannette Duncan is good: "If you have anything of importance to tell me, please, PLEASE begin at the end!" So here is our conclusion:

Breast cancer is a largely PREVENTABLE disease, and we reach that good news because of our finding that a large share of recent and current breast cancer in the United States is CERTAINLY due to past medical irradiation of the breasts with x-rays at all ages, including infancy and childhood. Much of today's radiation dosage is preventable, without any interference with necessary diagnostic radiology, and hence many future breast cancers need not occur.

What do we mean by "a large share" of recent and current breast cancer?

Our estimate is that about three-quarters of the current annual incidence of breast cancer in the United States is being caused by earlier ionizing radiation, primarily from medical sources.

We will show that the recently growing incidence is not mysterious, and that if we wish to understand why the incidence has been growing, we must look to radiation events in the life of women 15-25-35-45 and more years before breast cancer diagnosis.

Moreover, there is recent evidence about induction of EARLY-onset breast cancer by radiation (Chapter 3).

There are many stories in this book, but no villains. The cast of historical characters is interesting, impassioned, and sometimes very wise.

No one meant to do any harm. On the contrary. After discovery of the x-ray in 1895 and of radium in 1898, radiation was tried out widely in medicine, right up to recent times, in the hope of RELIEVING a great variety of human afflictions.

Some radiation therapies were (and are) clearly effective (and this book is highly complimentary about such uses). Some other therapies, clearly not effective, have been discontinued.

But usefulness is not always clear-cut in medicine. For example, users reported benefits which others could not see, regarding one type of x-ray therapy which was used for infants and children from 1911 to almost 1960.

The finding of this book constitutes an example of what can happen from exposing people to new agents, such as x-rays, when no one KNOWS the long-term consequences.

Readers will see the innocent enthusiasm, the repeated assurances that the procedures were safe, and the power of the "technological imperative" to suppress the idea that there might be a problem with anything as wondrous and potentially useful as x-rays.

This is a story of "disaster creep" — a massive problem creeping up on society without any recognition.

In science, every important discovery should be challenged and checked by others, and our finding certainly will be. We will welcome the genuine, thoughtful critiques. And we expect our finding to be validated. We arrive at our startling conclusion after UNDERestimating the past dosage of x-rays, and after using conversion-factors (conversion from dose to subsequent cancers) which derive from real-world observations.

There is just no doubt that past radiation exposure accounts for a major share of our recent and current breast cancer problem. The evidence for our finding is overwhelming if one simply looks.

Many will look thoughtfully at the input to this study but there will be exceptions. We expect our finding to be automatically rejected by some who merely WANT it to be faulty and who will comment upon it without even reading this book.

If breasts could talk, they might say, "Read first, judge second, and please start now!"

Part 2. For Whom Is This Book Intended?

This book is intended for anyone interested in breast cancer, and its prevention. Interest in the problem is the only requirement. The book is for medical professionals AND for individuals with the greatest personal concern: Women in general and their families.

Readers do not need to know every medical term in the stories, because the MEANING of the stories will be clear anyway. No medical skill or knowledge is essential to understand what will be presented.

Many chapters will begin with a description of what happened, and will end with specific calculations based on the events. Of course, many readers will skip the numbers. The "easy readers" should feel no guilt for skipping the latter part of various chapters. Lots of professionals, also, read scientific journals without ever examining the calculations and tables there.

But numbers are in journals, and also in this book, for a very important reason: To ALLOW people to check for themselves exactly how the quantitative conclusions were reached, and to evaluate the validity for themselves.

Part 3. An Astonishing Statement in a Fund-Raising Appeal

I've recently received in the mail a request for funds to help breast cancer research. It said: "Breast cancer is THE most commonly diagnosed cancer in American women today. It is THE leading cause of death among women ages 40 to 44, and the leading cause of cancer death in women 20 to 54."

No argument about that. Every part of that statement makes it all the more important for women to know precisely why we say that breast cancer is largely preventable. Then the letter added:

"What's worse, even the best doctors have no idea what causes breast cancer or how to cure it." Cure is indeed problematical, and when successful, the process itself can be highly unpleasant. All the more reason why prevention is so very important.

But how can anyone in 1994 say that "even the best doctors have no idea what causes breast cancer"? This error also went out over NBC national news during October 1994, in the television network's coverage of Breast Cancer Month.

In reality, medical science has clearly known for some 20 years already that ionizing radiation is a prominent and proven cause of breast cancer. Ionizing radiations include x-rays and gamma rays, as well as beta, alpha, and some other high-speed particles. (Radium is used in medicine as a source of powerful gamma rays.)

We think "the best doctors" do indeed know about the role of ionizing radiation as a prominent, proven cause of breast cancer, but it is astonishing that both lay and medical sources COMMONLY fail to mention this outstanding fact of medical science: Past medical exposure to ionizing radiation, 10, 20, 30, 40, and more years back in a woman's life, can cause breast cancer.

Radiation exposure in the first few months of life may be the most serious in causation of later breast cancer. In fact, irradiation of the breasts between age 0 (newborn) and age 9-years may cause MANY-fold more cases of breast cancer, over the subsequent lifetime, than does irradiation of women over 40 years of age with the same amount (dose) of ionizing radiation.

The Current Size of the Problem, USA

Today, it is estimated that one woman out of every nine in the USA will develop breast cancer sometime during her lifespan. The breast cancer problem is reflected in the estimates below, of breast cancer incidence in the USA (derived by the American Cancer Society from government data). The numbers exclude "in situ" cases. The rapidly rising numbers below reflect diagnosis, not death.

As so many families know already, diagnosis in itself brings severe consequences, even if a woman dies of something else in the end. The numbers on the right show that the growth of the female population can explain only a small part of the rising incidence of breast cancer. (The tabulation below is expanded in Tables 1 and 2, which are located after the final chapter.)

1970: 68,000 cases diagnosed; females of all ages = 104,309,000
1975: 88,000 cases diagnosed; females of all ages = 110,401,000 est.
1980: 108,000 cases diagnosed; females of all ages = 116,493,000
1985: 119,000 cases diagnosed; females of all ages = 122,474,500 est.
1990: 150,000 cases diagnosed; females of all ages = 128,454,000
1994: 182,000 cases diagnosed; females of all ages = 133,194,000

Part 4. How Do We Know that Radiation Is a Cause of Breast Cancer?

Every once in a while, a massive step forward in medicine is taken by the oldest technique in medical practice the careful taking by a physician of a patient's medical history. Such an event of landmark proportions is represented by the observations of Dr. Ian MacKenzie, a physician in Nova Scotia, Canada.

In 1961, a woman with a rapidly growing breast cancer came to his office. He noticed that her cancer had occurred in the upper inner quadrant of her right breast, and that her skin over the right chest wall, breast, and sternum showed signs of dermatitis (skin inflammation).

MacKenzie questioned her carefully about her history, and learned that she had been treated 14-15 years earlier for pulmonary (lung) tuberculosis. In those years, a common practice was to let one of the lungs rest, by collapsing it with an injection of air between the chest wall and the lung. This procedure was called artificial pneumothorax therapy, and in her case, it took place over 46 months. Each time she had a re-fill of air into the chest, the status of the lung was checked with fluoroscopy, before and usually after.

Fluoroscopy is also called roentgenoscopy, in honor of Wilhelm Konrad Roentgen, who discovered x-rays in 1895. In roentgenoscopy, examination of a patient with x-rays takes place while the x-ray beam stays "on," so that the physician can observe what happens when the patient or the patient's organs are in motion.

Roentgenoscopy is thus very different from roentgenography, which is the use of x-rays to expose a sheet of film (or other types of image-receivers) to produce the usual x-ray picture. Roentgenoscopy, requiring no development of film, produces information immediately.

When Dr. MacKenzie obtained his patient's sanitarium records, he learned that she had had at least 200 fluoroscopic examinations during her treatment. The patient remembered that her skin changes began during this period, too. Dr. MacKenzie recognized that she had radiation dermatitis, and he began to suspect that breast exposure to x-rays might also account for her breast cancer.

To check on this idea, Dr. MacKenzie studied almost 800 women who had been treated for tuberculosis in one sanitarium during 1940-1949. The startling results were published in 1965.

Of 510 women who did NOT receive artificial pneumothorax treatment and therefore did not have repeated fluoroscopies, one woman had subsequently developed breast cancer by the time of Dr. MacKenzie's study. This is a rate of (1 woman / 510 women), or 0.00196.

Of 271 women who DID receive artificial pneumothorax treatment with multiple fluoroscopies, 13 had developed breast cancer by the time of Dr. MacKenzie's study. This is a rate of (13 / 271), or 0.04797. The breast cancer rate in the irradiated group was (0.04797 / 0.00196), or 24.5 times the rate in the non-irradiated group. In his paper (p.7), Dr. MacKenzie said:

"From the evidence presented, it would appear to be a reasonable conclusion that the well-recognized role played by ionizing radiation in the development of certain other forms of malignant disease can be extended to include carcinoma of the breast in the circumstances presented by these cases."

If pulmonary tuberculosis itself were the cause of the breast cancers, then the irradiated and non-irradiated cases should have had similar breast cancer rates, as Dr. MacKenzie commented. Dr. MacKenzie's finding caused quite a "stir" in radiation circles.
1965 (March): Ian MacKenzie, "Breast Cancer Following Multiple Fluoroscopies," British Journal of Cancer 1965, Vol.19: 1-8.

Soon thereafter, C.K. Wanebo and colleagues, studying the survivors of the atomic bombings at Hiroshima and Nagasaki, and stimulated by the MacKenzie work, launched an investigation of breast cancer in those survivors. In 1968, they published confirmatory evidence of human breast cancer induction by ionizing radiation.

In 1969, Myrden and Hiltz extended the follow-up time for MacKenzie's 1965 study. And in 1970, Arthur Tamplin and I used the MacKenzie and Wanebo data to quantify the dose-response for radiation-induced breast cancer. We showed in The Lancet that the breast cancer risk from ionizing radiation was quite serious indeed.

Proven, and Then Forgotten?

In the years which have followed MacKenzie's 1965 paper, numerous studies have confirmed and quantified the induction of breast cancer by ionizing radiation. For the convenience of readers, we have identified a number of those papers by prominently flagging them with the symbol "#" in our list of references.

Many of these studies have been analysed in Gofman 1981 and in Gofman 1990. In 1994, even further confirmation became available in the latest reports on cancer incidence in the A-Bomb Survivors (Mabuchi; Thompson; Tokunaga).

The radiation-causation of human breast cancer is not in dispute. Nonetheless, it is commonly forgotten in discussions about the alleged mystery of breast cancer causation.

Part 5. What about Other Potential Causes of Breast Cancer?

Cancer — not breast cancer alone — is now considered to be a genetic disease. It is thought that a tumor develops in stages from a single cell, as the cell and some of its descendants accumulate a set of several "genetic lesions." A lesion is an injury or loss of function. Genetic lesions are those which occur in the genetic molecules — namely, in the DNA molecules which control a cell's proper operation, including the accuracy and appropriate rate of the cell's division. Genetic lesions in a cell can occur at any age.

Inherited diseases are properly called genetic diseases. They occur because offspring receive certain genetic lesions in the DNA which they inherit from their parents. (Mother and father do not often transmit the SAME lesions, however.) Inherited genetic lesions are present in the fertilized human egg. Since every cell we have is descended from the fertilized egg, the lesion is present in every cell.

By contrast with an inherited lesion, a genetic lesion which occurs in childhood or adulthood is present only in the cell where it took place, and in cells descended from the altered cell, but it is not present as an all-cell lesion. So, inherited diseases are genetic, but not all genetic diseases have to be inherited. The responsible genetic lesions can occur after conception.

With respect to cancer, it is thought that cells become malignant only after they have accumulated several carcinogenic lesions (many estimates range from four to ten lesions). Some of the lesions may be inherited, and others may occur at any age after conception.

Individuals who inherit one or more carcinogenic lesions in EVERY cell, have an increased chance that SOME of their cells will accumulate a complete set of the necessary lesions during their lifetimes. Such people are born "predisposed" to develop full-blown, clinical cancer.

Interaction of Inheritance and "Other Forces"

Almost certainly, inherited carcinogenic lesions have a range from weak to strong. The famous lesions are the rare inherited ones which confer a high chance of cancer in a specific organ, with the clinical cancer often occurring at a very early age. We call those "destiny" lesions, and the weaker ones "predisposing" lesions.

The inherited "destiny" lesions are estimated to account for five to ten percent of human cancer. For breast cancer, the estimate is about ten percent. Even a "destiny" lesion may need help from other forces, in order to create some cells with the COMPLETE set of genetic lesions required for full-blown cancer. By "other forces," we mean to include agents such as x-rays, viruses, or certain chemicals.

An inherited "predisposing" lesion, by definition, needs help from other forces in order to cause a cancer.

Do such other forces, acting in the absence of INHERITED carcinogenic lesions, ever produce the complete sets of lesions required for malignancy? At this time, there is no way to know how often this happens, if ever. It may turn out that cancer almost NEVER develops in the absence of an inherited "head start" ... and almost ALWAYS requires the interaction of inherited lesions with other forces.

The bottom line on inheritance and other forces is this:

A very large part of the cancer problem can be eliminated, if people CORRECTLY identify and eliminate the non-inherited forces which act alone or act in concert with inherited genetic lesions, in producing malignancy.

This book shows that past exposure to medical x-rays is a MAJOR non-inherited cause of the breast cancer which has occurred, is now occurring, and is already committed to occur in the future in the USA.

Readers who follow the stories, chapter by chapter, will end up realizing that medical radiation is surely a non-inherited cause of OTHER cancers, also. How large the share is, for other cancers, remains to be evaluated.

And What about Pesticides, Hormone Pills, Diet, and EMFs?

There is nothing about the finding of this book to imply that ionizing radiation is the ONLY cause of recent breast cancer.

Many non-inherited forces, including pesticide by-products, hormone pills, diet, exercise, EMFs (electromagnetic fields and "transients"), and several additional factors, have been implicated by epidemiologic studies as potential contributors to recent rates of breast cancer. (Epidemiology is a science which tries to find the causes of diseases, by comparing their frequencies in various groups of people.)

Do we dismiss these other forces? Not at all. Even agents and behaviors which cause no permanent genetic lesions may accelerate a developing cancer in several ways without casting any doubt upon the multi-step genetic model of cancer development. The power of such promoters may depend on the presence of genetic lesions.

Indeed, we take this opportunity to say that we are particularly concerned about the question of EMFs, to which human exposure is likely to INCREASE in future years. We highly recommend a collection of papers on EMFs and breast cancer (Slesin 1994).

With respect to ionizing radiation, the proof that extra exposure is a cause of cancer (including breast cancer) comes from studies where all sorts of ADDITIONAL non-inherited causes may have been operating too. The point is this:

In any valid epidemiologic study, those other carcinogens are acting EQUALLY upon the irradiated groups and upon the non-irradiated groups. Thus, the EXTRA cancers in the irradiated groups can be attributed to the extra radiation, but the REST of the cancers are due to something else (such as equal exposure, on the average, of all the study-groups to chemicals, EMFs, or prior exposure to radiation-sources other than the source studied).

There is no inherent conflict or competition between carcinogens. The multi-step genetic model of cancer development "permits" contributions even to a SINGLE CASE of cancer, from heredity, ionizing radiation, viruses, and chemicals (for example). It is correct to say that each contributor CAUSED the cancer, if the case would not have occurred when it did, without that contributor.

The finding of this book is that an estimated 75 percent of recent and current breast cancer cases would not have occurred as they did, in the absence of earlier medical (and other) irradiation.

CHAPTER 3: Early-Onset breast cancer: Evidence on Radiation-Induction

Recent evidence, discussed below, underscores the importance of acting upon the finding of this book, if prevention is everyone's goal. So that all readers (including the "easy readers") can contemplate the meaning of this new evidence, we introduce the units in which radiation doses are measured.

Part 1. Dose-Units, Especially "Medical Rads"

The term "medical rad" is the one which we use in reaching the finding of this book. To show what it means, we have to cover some other units.

RADS. The "rad" is a unit in which amounts (doses) of ionizing radiation are measured, the way "dozen" measures an amount of eggs. Rad is the abbreviation for "radiation absorbed dose." A rad is really just a ratio of energy delivered by ionizing radiation, per gram of irradiated cells or tissue. A rad is 100 ergs of energy per gram a definition which NO reader needs to remember. One thousandth of a rad, or 0.001 rad, is a milli-rad. An effort is underway to re-name the rad as a centi-gray (cGy) and to call 100 rads a gray (Gy). We and many others prefer to stick with rads.

ROENTGENS. The Roentgen is a unit for measuring ionization in air; a few reports also use it for doses inside the body. The abbreviation for Roentgen is R (but a small "r" was customary in the older literature). Under common medical circumstances, an entrance dose of 1 Roentgen at the skin gives a breast-tissue dose of about 0.69 rad, when the beam is traveling from front-to-back of a patient. The Roentgen is the dose-unit often used to describe x-ray dosage from fluoroscopy. In the 1930-1935 era, many fluoroscopy machines could generate beams with dose-rates like 100 Roentgens per minute (Braestrup 1969).

REMS. Another unit is called the rem, an abbreviation for "roentgen equivalent, man." The rem can indicate that adjustments have been made for the non-standard "quality" of some radiations. Usually (but not always) the standard is an x-ray of 100 to 400 KeV. An effort is underway to re-name the rem as a centi-sievert (cSv) and to call 100 rems a sievert (Sv).

MEDICAL RADS. Per rad, gamma rays from an atomic bomb are about half as harmful as x-rays from medical irradiation, so 1.0 rad of A-bomb gamma radiation could be called 0.5 rem. We avoid rems in this book by converting all doses into "medical rads." Hence, 1.0 rad of A-bomb gamma radiation is called 0.5 medical rad.

Some Very Common Radiation Dose-Levels

• NATURAL BACKGROUND RADIATION. The typical annual dose from natural background radiation, excluding doses from inhaled radon, is about 0.1 rem or 100 milli-rems (BEIR 1972, p.50; BEIR 1990, p.18). The dose per year rises with altitude.

Because the natural background dose is mostly from gamma and cosmic radiation, its medical equivalent per year is about 0.05 medical rad (50 medical milli-rads). In a 70-year lifespan, the cumulative dose is about 3.5 whole-body medical rads. A whole-body dose is received by all parts of the body, in contrast to a partial-body dose.

The natural dose-rate per MINUTE is of interest, for comparison with dose-rates from fluoroscopy. Nature's dose-rate per minute is (0.05 medical rad / year) times (1 year / 525,600 minutes), or 0.000000095 medical rad per minute from natural background radiation. If we round this off, it is about one ten-millionth of one medical rad per minute. At this dose-rate, only a tiny fraction of cells is irradiated per minute.

• AIRLINE TRAVEL. The extra radiation dose, from flying between the east and west coasts of the USA, is about 0.3 milli-rem (0.0003 rem) per HOUR of commercial flying. For a ten-hour roundtrip, the extra dose would be about 3 milli-rems (0.003 rem). It would require about 3,300 flying-hours to receive 1.0 extra rem of whole-body irradiation --- equivalent to about 0.5 extra medical rad. Dose-rates from flying vary with altitude and latitude.

Part 2. The Dose Which Doubles the Rate of Early-Onset Breast Cancer

Ordinarily in epidemiological studies of cancer development from radiation, one faces the "small numbers problem": An insufficient series of cases in the relatively EARLY follow-up period to permit a reliable conclusion. So time is allowed to run, to accumulate additional cases ("statistical power"). And then all the cases --- short latency and long-latency cases, combined --- are examined together for such issues as cancer increase per rad of dose.

But WHAT IS LOST, within the accumulated total, is any evaluation of whether the "early-onset" cases are different from the other cases. From here on, the cases diagnosed before age 35 will be called "early-onset" cases.

With follow-up of the A-bomb survivors now complete for 1950 through 1985, there may be enough total cases of breast cancer to separate the early-onset cases from the others, and to compare them for induction-rate per rad of irradiation.

In 1993, Charles Land, Masayoshi Tokunaga, and additional RERF analysts, made a brief report in the Lancet, entitled "Early-Onset Breast Cancer in A-Bomb Survivors" (Land 1993). By extracting the pertinent data from the figure in their 1993 paper, we can tabulate their findings in the nearby box. They are remarkable results, to say the least!

In their 1993 paper, Land et al. are reporting exclusively on female A-bomb survivors who received the bomb exposure before the age of 20 years. Although Land et al. do not say so, the number of females who were exposed by the bombs below age 20 was approximately 12,000, and their average age at the time of bombing was about 10 years old (calculated from Gofman 1990, Table 26-F).

There are 205 incident cases of breast cancer, reported between 1950-1985 for this group. The cases are segregated by Land et al. into two main groups: Women whose breast cancers occurred before age 35 years constitute one group, and women whose breast cancers appeared after age 35 years, the other group. We repeat: All the women were less than age 20 at the time of exposure.

In the boxed tabulation, the entries for "fractional increase ... per rad" indicate a spectacular difference between early-onset cases versus cases occurring at age 35 and beyond. The difference is treated as real (not spurious) in both Land 1993 and Tokunaga 1994.

We shall propose an explanation of the difference in Part 4. But here, we will focus on the breast-dose which, if delivered sometime before age 20, can DOUBLE the rate of early-onset breast cancer. This value can not change with any future observation of the A-bomb survivors, because the story for EARLY-onset cases was over when the youngest survivors (newborn in 1945) passed the age of 35 in 1980.

• TABULATION BASED UPON LAND ET AL., 1993.

	Average Age When Breast Cancer Occurs	Number of Breast Cancer Cases	Fractional Increase in Breast Cancer Rate over Spontaneous Rate per rad
Breast Cancers Occur Before Age 35 years	32 years	27	0.136 13.6 %
Breast Cancers Occur After Age 35 years	41 years 49 years 57 years	80 85 13	0.013 1.3 % 0.024 2.4 % 0.017 1.7 %
Sum of cases,	bomb-exposed	women	205 cases.

The "Doubling Dose" for Early-Onset Breast Cancer

The dose which doubles the spontaneous frequency of early-onset breast cancer is the dose which causes a 100 % increase in its spontaneous rate. Therefore, to estimate how many rads would cause a 100 % increase, we divide 100 % by 13.6 % per rad (from the boxed tabulation). Thus, 7.35 rads, received before age 20, is the approximate doubling dose for early-onset breast cancer.

The doubling dose for early-onset breast cancer is even lower when we consider medical x-ray radiation, or beta particles of energy comparable to such x-rays. The medical rad has approximately two times the effectiveness of A-bomb radiation from which Land, Tokunaga, and colleagues developed their findings.

Therefore, we must warn that the dose of medical rads required to double the spontaneous rate of early-onset breast cancer must be in the neighborhood of only 3.68 medical rads, received sometime before age 20.

As readers will see in Sections 2 and 3 of this book, such doses and far higher ones have been commonly received during childhood from certain medical procedures and we do NOT mean doses from radiation therapy after a cancer has already occurred.

Part 3. A Test for Agreement about the Magnitude of Risk

Below, we will show the good agreement between RERF's quantification of risk (by Land, Tokunaga, et al) and our own independent analysis of 1990. The "easy readers" of this book may wish to skip to Part 4 or Part 5, but others will find Part 3 very interesting.

Our analysis used the data on cancer deaths (all types) from 1950-1982 in the A-Bomb Survivors, and the RERF analysis used exclusively the breast cancer incidence from 1950-1985 among the A-Bomb Survivors.

Both analyses (Gofman and RERF) are finding out the "fractional increase or percent increase above the spontaneous rate, per rad" a concept which we named "the K-value" simply for the sake of brevity. Tokunaga et al. call the same thing "Excess Relative Risk," or ERR.

Based on the linear dose-response in Tables 15-G and 15-H of Gofman 1990, our K-value estimate for females exposed at ages 0-9 years is 0.01922 (the same as 1.922 %). Age 0 means from birth to the first birthday.

For exposure at ages 10-19, the K-value is 0.01097 (or 1.1 %). When the two values are weighted by the number of cases, the average is 0.01265, or 1.265 % per rad for exposure at ages 0-19. This value is for ALL types of cancer, combined.

For breast cancer alone, the K-value is 2.524 times the value for combined types (Thompson et al 1994, pages S26, S49, S61). Multiplying the 1.265 % per rad for all cancers, by 2.524 to adjust for breast cancer alone, we obtain a K-value of 3.2 % per rad for breast cancer, when bomb-exposure occurred at ages 0-19 years.

The comparable K-value from RERF's own analysis is 2.41 % per rad from Tokunaga 1994, p.215, Table VI. RERF's value is derived from observations of cancer incidence, whereas our value is derived from observations of cancer mortality. When our 3.2 % is divided by their 2.41 %, we see that one estimate differs from the other by only 33 % . The two separate analyses are in remarkably close agreement.

The similarity in estimates is supportive of the concept that, when extra radiation induces extra cancers, it induces cancers which are fatal and non-fatal in the same proportion as occurs without the extra exposure to radiation.

Part 4. Early-Onset Cases vs. Later Cases: Why Such a Difference?

If readers look back in Part 2 at the boxed tabulation, they will see the column for "average age when breast cancer occurs" for 205 of the A-bomb survivors irradiated between birth and age 20. For cases diagnosed at an average age of 32, the percent increase per rad above the spontaneous rate is 13.6 %, whereas the percent increase per rad is DRAMATICALLY LOWER if diagnosis occurs at the average ages of 41 years, or 49 years, or 57 years.

What accounts for the striking difference? Is there some big biological difference between the radiation-induction of breast cancer for cases which appear before age 35, compared with the radiation-induction of cases which appear after age 35? Is there some altered response (to irradiation during childhood) in the irradiated HOSTS after they pass age 35? Various possibilities are discussed in Tokunaga 1994 (pp.221-222).

We propose a relatively simple explanation. Our figure, "Three Curves with a Story," demonstrates how the observed difference could arise.

Three Curves with a Story

Curve B = breast cancer rate in women irradiated below age 20, by an unspecified dose.
Curve A = spontaneous breast cancer rate in comparable non-irradiated women.
Curve C = relative risk (Curve B / Curve A).

Three Curves with a Story: Age at breast cancer Diagnosis, in Years.

Age at Breast Cancer Diagnosis, in Years.

Age	A	B	C	Age	A	B	C
29	0	0		50	42.5	102	2.4
30	0.1	1	10.0	51	44.0	104	2.4
31	0.2	2.5	12.5	52	45.0	107	2.4
32	0.2	4.0	20.0	53	46.5	108	2.4
33	0.6	7.5	12.5	54	47.0	110	2.4
34	1.0	11.0	11.0	55	47.5	112	2.4
35	2.0	14.0	7.0	56	48.0	113	2.4
36	3.5	20.0	5.7	57	48.5	114	2.4
37	5.05	25.5	5.0	58	49.0	114	2.3
38	7.5	32.0	4.3	59	49.3	114	2.3
39	9.5	39.5	4.2	60	49.6	114	2.3
40	12.0	45.5	3.8	61	49.7	114	2.3
41	15.0	54.0	3.6	62	50.0	114	2.3
42	18.0	61.0	3.4	63	50.0	114	2.3
43	21.5	68.0	3.2	64	50.0	114	2.3
44	25.0	75.0	3.0	65	50.0	114	2.3
45	28.0	80.0	2.9	66	50.0	114	2.3
46	32.5	86.0	2.6	67	50.0	114	2.3
47	35.5	90.0	2.5	68	50.0	114	2.3
48	38.5	94.0	2.4	69	50.0	114	2.3
49	41.5	98.0	2.4	70	50.0	114	2.3

Who Are These Curves?

• CURVE A: In the nearby figure [above], Curve A depicts a SPONTANEOUS breast cancer rate beginning to rise when women reach the age of about 30. We wish to emphasize that Curve A is a "generic" or illustrative curve, with imaginary rates of new cases (per 10,000 women) on the vertical axis. The reality-based aspect of Curve A is its depiction of a rise which is gradual, then steep, and then gradual again.

For ages 20 through 29, the spontaneous frequency of breast cancer is very low (shown as "zero" rate). Then, for ages 30, 31, and 32, we have elevated each data-point (really, data-symbol) SLIGHTLY above the baseline. At age 33, we show the rate of new cases starting to increase in each successive year, with the amount of annual increase greater (steeper) between ages 35 and 50 than between ages 50 and 60, for example. The rates plotted as Curve A are tabulated in the box underneath the figure.

• CURVE B: Curve B depicts the corresponding breast cancer rate in a comparable group of women who received breast irradiation between birth and age 20. Again, we show IMAGINARY rates of new cases (per 10,000 women) on the vertical axis, and we have not specified any particular radiation dose.

What we are showing, however, is reality-based: Starting at age 30, the irradiated group shows a rate of breast cancer which is HIGHER than the spontaneous rate. The real-world observations of a higher rate were discussed in Part 2.

Among the irradiated A-bomb survivors who were ages 0-19 during the bombings, there are 27 cases of early-onset breast cancer --- and all but 2 or 3 of those cases were diagnosed when the women were ages 30 through 34 (Tokunaga 1994, p.214). There are 178 additional cases diagnosed after age 35 in that group.

What we want to explain is why the percent increase per rad is so much higher for the cases diagnosed at the average age of 32 (the early-onset cases) than for cases diagnosed later. Curve C depicts the question.

• CURVE C: Curve C shows the result when each cancer rate of Curve B, for irradiated women, is divided by the corresponding (and lower) cancer-rate of Curve A, for non-irradiated women. The values are also tabulated beneath the figure. These ratios are the relative rates, or Relative Risks (RR), which quantify how many TIMES higher the exposed rate is than the spontaneous rate.

We plot the RR values as Curve C, which uses the scale of the vertical axis as an "all-purpose" scale (just don't say "per 10,000 women").

At age 32, the tabulation shows that the irradiated rate is 20 times higher than the spontaneous rate. To transform this Relative Risk of 20 into percent increase per rad (K-value), we just subtract 1.0 from the Relative Risk and then divide 19 by the dose in rads. Example:

If the average dose which produced Curve B were 110 rads, then the fractional increase per rad for cases diagnosed at age 32 would be (19 / 110 rads), or 0.173 per rad which is the same as 17.3 % per rad.

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Footnotes

1 Breast Cancer Mortality After Diagnostic Radiography: Findings from the U.S. Scoliosis Cohort Study published in The Spine in August 2000

Related section

Causes of Cancer