War on Cancer

by Ralph W. Moss, PhD

Falling Down the Rabbit Hole!

Scientists studying triple-negative breast cancer at Vanderbilt University recently made a disturbing discovery. Even after receiving chemotherapy before surgery, most patients still had multiple genetic mutations in their tumor cells. Justin Balko, PhD and Carlos Arteaga, MD, presented these findings at the San Antonio Breast Cancer Symposium, Dec. 4–8.

Triple-negative breast cancer patients are routinely treated with chemotherapy to shrink their tumors prior to surgery. This is called neoadjuvant chemotherapy (NAC). But most still had multiple genetic mutations in their tumor cells, according to a study by Vanderbilt-Ingram Cancer Center (VICC) investigators.

“The standard of care for many patients with triple-negative breast cancer is to administer chemotherapy before surgery to shrink the tumor,” said Balko. “Unfortunately, about 70% of patients still have some residual disease at the time of surgery, despite treatment.”

Balko looked at residual tumor tissue from 114 patients with triple-negative breast cancer after they received NAC. They evaluated DNA from 81 tumors and examined 182 oncogenes and tumor suppressors that are often altered in human cancers.

Instead of finding similar genes affecting the patients, however, they found a diverse set of altered genes.

“We already knew that triple-negative breast cancer is driven by a diverse group of genetic alterations,” Balko said. “So, in one way, we fell further down this rabbit hole….”

But putting a positive spin on this diversity, she said that they found some promising therapeutic targets.

Tip of the Iceberg

These genetic mutations are just the tip of an iceberg. An article in Science last year contained an article with the astonishing assertion that in many cases of cancer there were thousands of separate mutations in each tumor.

We now know that there are usually between 1,000 and 10,000 somatic substitutions [mutations] in the genomes of most adult cancers, including breast, ovary, colorectal, pancreas, and glioma [brain]. … There are cancer types that generally carry relatively few mutations–for example, medulloblastomas, testicular germ cell tumors, acute leukemias, and carcinoids … whereas others, such as lung cancers and melanomas, have many more mutations (occasionally more than 100,000). … Even within a particular cancer type, individual tumors often display wide variation in the prevalence of base substitutions. (Stratton 2011)

Imagine, then, trying to devise a treatment regimen that targets thousands of separate mutations! This is what Balko meant when she referred to falling down the rabbit hole. Scientists who believe the somatic mutation theory of cancer are facing a dismaying prospect. Some rare types of cancer may yield to genetically-based treatments. But the typical kinds of cancer have too many mutations to cover with even a panoply of drugs. By contrast, if scientists focus on the abnormal metabolism of cancers they will find a few conspicuous targets that are common to most cancers. They can then devise drugs and other methods of modifying how cancer cells derive their energy–such as the excess uptake of glucose.

Chemo Assay Yields Better Results

DiaTech is a company that also has a Vanderbilt connection. The company that provides the MiCK assay, a chemosensitivity test for the live tissues of cancer patients. This test helps determine, on an individual basis, which drugs are likely to work and which will not work. Although in the past the “cancer establishment” has scorned this type of test, there is growing evidence that they yield better than average results.

At the San Antonio cancer symposium, DiaTech scientists offered evidence of this. When doctors used the MiCK assay, they changed their treatment plan 68% of the time. They achieved disease control 81% of the time when they used the assay vs. 25% when they did not, a huge 56% advantage. Overall survival was 16.8 months in the assay-guided patients vs. 13.1 months in those who did not use the assay. The median time-to-recurrence when the MiCK assay was used was 7.4 months vs. 2.2 months if the physician did not use the assay.

One interesting aspect of this study is that it did not direct oncologists in how to treat the patients. The authors felt that they would produce a more valid test of how the assay would be used in actual practice, where oncologists have complete discretion in treatment planning.

I have written a book on this general topic, called Customized Cancer Treatment. It is available through Amazon.

Metformin May Boost Survival in Ovarian Cancer

Metformin is a drug commonly used to treat type 2 diabetes. It decreases the amount of circulating glucose in the blood. Since cancers mainly feed on glucose, there has been some speculation that metformin may have a beneficial effect in cancer patients as well. The drug is ultimately derived from an herb called French lilac or goat’s rue (Galega officinalis).

Metformin, a commonly prescribed oral drug for diabetes, may improve survival in women with ovarian cancer. This was the conclusion of a December 2012 study from the Mayo Clinic (Rochester, MN). The case control study was published in Cancer. (Kumar 2012)

Women with ovarian cancer who received metformin were compared with women with ovarian cancer who did not receive the herb-derived drug.

In a preliminary analysis patients who received metformin had a 5-year survival of 73%, vs. 44% in those who did not. Even when age, disease stage, histology, and so on, were taken into account the difference remained similar. In this more rigorous analysis, metformin patients had 5-year disease-free survival of 67% vs. 47% in those who did not get the drug, an absolute advantage of 20%!

Although not a randomized trial, this retrospective study did show an association between metformin intake and the survival of ovarian cancer patients. The Mayo Clinic authors concluded that metformin was worthy of a more rigorous clinical trial in this situation.

First Name Shridhar pointed out that although metformin is generally safe, it does have some adverse effects, including the possibility of nausea/vomiting, cramping, abdominal pain, and diarrhea. For that reason she does not recommend using it until the completion of hoped-for clinical trials.

Is Laetrile a Vitamin?

It is an amazing that although the scientific community rejected the claim that laetrile (the cyanogenic glycoside, amygdalin) is a vitamin, a broad section of the public still accepts it as “vitamin B17.” A Google search for vitamin B17 returns over 400,000 hits. So it is worth examining this claim in some detail. After all, it is no small matter of whether such a vitamin exists and should be eaten by health-conscious people.

The idea of laetrile, or amygdalin, as an anticancer vitamin originated with Ernst T. Krebs Jr. around 1970. It then spread all over the world as the laetrile movement picked up steam.

Laetrile’s use raised many scientific issues, as well as political, socioeconomic, and ethical ones. Although the movement per se is gone, and many of the key proponents have passed away, these issues remain alive. I have much to say on each of the scientific issues involved in this controversy, but right now I would like to address myself to the question of whether laetrile can be considered a vitamin.

The essence of Krebs’s claim was epidemiological in nature. He insisted that populations that consume relatively large amounts of laetrile have very little, if any, cancer, while those who had given up the habit of eating laetrile-rich foods suffered from devastating levels of the disease.

His prime examples were the Hunza people of Pakistan and the Inuit people of the Arctic. According to him, both these populations had low rates of cancer and also ate a lot of laetrile-containing foods. Krebs linked the Hunzas’ supposed good health to their consumption of apricot kernels:

Tribes in the Karakorums of West Pakistan … rely upon a diet carrying as much as 250 to 3,000 mg [per day] of nitriloside [laetrile] in a daily ration. All populations living close to a neolithic level appear to be characterized dietarily by a similarly high consumption of nitriloside-rich foods. Civilized, Westernized or Europeanized man, on the other hand, relies on a diet that probably provides an average of less than 2 mg of nitriloside a day.

The Hunzas, Krebs said, ate lots of apricots and especially prized the apricot kernel (a rich source of laetrile). He wrote:

[U]pon investigating the diet of these people we found that the seed of the apricot was prized as a delicacy and that every part of the apricot was utilized. We found that the major source of fats used for cooking was the apricot seed, and that the apricot oil was so produced as inadvertently to admit a fair concentration of nitriloside or traces of cyanide into it.

However, firsthand observers contradicted this account. According to the physician John Clark, MD, writing in 1956 in The Lost Kingdom of the Himalayas:

Hunzas eat the apricots fresh or dried, and crack the seeds open to obtain the almond-like nuts. … The sweet apricot nuts are eaten plain. The bitter ones are ground with stone mortars … and the oil is squeezed by hand from the resulting nut meal. This oil is highly poisonous. It is used for fuel in the little shallow saucer lamps, with a cotton twist for a wick” (emphasis added).

The bitterness of apricot kernels, and their resulting oil, is entirely dependent on its laetrile content. Thus, while it is probably true that Hunzas ingested more laetrile than Western people, they also took active steps to minimize their exposure to it. They basically used it for light and heat, not nutrition.

In reality, Hunzas had many of the same diseases as the rest of mankind, and (despite claims to the contrary) no particular health or longevity. As to cancer, Clark does not mention it and Krebs may be right in stating that it was unusual there. But that situation was typical for almost all indigenous people eating a whole-foods diet in their native habitat. That said, there is no factual basis for believing that it was the ingestion of GCs from apricot kernels and other sources that kept these indigenous people relatively cancer free. This could have been the result of other nutrients or any combination of things that constituted a profoundly different lifestyle than the Western lifestyle of today.

The Case of the Inuit

Another one of Krebs’s favorite arguments concerned the Inuit:

For a period of at least 80 years the Eskimaux [sic] have been observed with even greater scrutiny by medical men, missionaries, teachers, traders and others for the specific purpose of attempting to discover the possible incidence of cancer among them. Despite such observations, no case of cancer has yet been reported among these two native populations [the Hunza people and the Inuit] while they lived on their native diet; however, in the case of the Eskimaux a number of cancer victims have been found among those who left their aboriginal dietary habits for a Westernized diet.

I believe the latter statement to be accurate. But the ethnologist and explorer Vilhjamur Stefansson (1879–1962) set forth contrary views in several fascinating books, including The Friendly Arctic and especially Cancer: Disease of Civilization?

With the adoption of Western ways, the “diseases of civilization,” including cancer, began to appear. In recent times (1998–2007), Inuit women had a 29% higher rate of cancer than the general Canadian population. (The male rate was 14% lower, mainly due to a lower rate of prostate cancer.) There is a particularly high rate of cancers of the nasopharynx, lung and bronchus, colorectal, stomach (males) and kidney and renal pelvis (females).¹ By contrast, there were many reports, from skilled medical observers, that the Inuit had virtually no cancer until the 1930s.

However, far from confirming Krebs’s theory, Stefansson reported that historically the Inuit diet was 90% meat and fish. They ate the meat of walrus, ringed seal, bearded seal, beluga whale, caribou, polar bear, muskoxen, birds (including their eggs), and fish. When they could, some of the Inuit also ate tubers, roots, and berries. But Stefansson reported that many of them would go six to nine months per year on nothing but flesh.

According to Krebs, despite their apparent lack of vegetative foods, the Inuit (a) actually ate an abundance of cloudberries (Rubus spectabilis); and (b) routinely ate the frozen contents of the rumen of caribou, which supposedly contained an abundance of laetrile.

Krebs wrote:

[W]e found that one berry grew abundantly in the Arctic areas and that this berry is extraordinarily rich in nitriloside. This is the salmon-berry, cloud-berry, or buffalo-berry (Rubus spectabilis). It is eaten by birds, animals and men. It is also incorporated into pemmican, which is eaten during all seasons of the year.

In The Friendly Arctic, Stefansson also mentions the Inuit’s ingestion of salmonberries. But his comments do not support Krebs’s interpretation. According to Stefansson:

It is well known that some Eskimo groups eat either no vegetable food at all or practically none. But in all parts where we have been, except in Coronation Gulf, they are fond of the berry known in Alaska as the “salmon berry,” and elsewhere as the cloud berry (Rubus chamaemorus Linn.).² We were astonished, especially my Alaska Eskimo companions, when we found that some of the Coronation Gulf Eskimos lived among an abundance of these berries and had never thought of tasting them. (p. 63; emphasis added)

Stefansson continued:

I should say that fully half the women [in Coronation Gulf] positively refused even to taste the salmon berry during the summer we spent with them. (p.64)

The anthropologists Harriet V. Kuhnlein and Nancy J. Turner, in Traditional Plant Foods of Canadian Indigenous Peoples: Nutrition, Botany and Use (1991), confirmed that cloudberries are “a staple of Indigenous Peoples of Northern Canada” but only from July to September. What about the other nine months of the year? During this time they eat no laetrile-containing foods.

Kuhnlein and Turner cite one report that some tribes, such as the Caribou and Copper Inuit, “seldom picked cloudberries although they were plentiful.”

In his 1964 essay Krebs also stated:

Obviously, animals such as the caribou are important in the diet of these people. In eating the caribou the frozen contents of the rumen or paunch are utilized as a salad and considered a delicacy. … One teaspoonful of such rumenal salad might be expected to carry 100 mg or more of nitriloside.

There is no reference given for the notion that the Inuit regularly ate “rumenal salad.” In their work, Kuhnlein and Turner comprehensively surveyed the diet of the Inuit (and some other indigenous peoples). But there is no mention there of a salad made from the animals’ rumen content.

I am sure that one might find instances of Inuits eating vegetables, even those containing laetrile, but there were clearly Inuit people who lived entirely without vegetables for nine months of the year or who chose to eat a diet with a total or near-total absence of laetrile. But far from being afflicted by a pandemic of cancer, there were no reported cases.

According to Krebs’ theory, cancer should have been nearly universal among certain Inuit tribes. Yet, according Stefansson and many other accounts, they were virtually free from cancer until the early 1930s. The cause was not the ingestion of laetrile, which probably had nothing to do with it. Many things changed in the transition from a hunter-gatherer society to a more modern society, albeit one existing at the geographical edge of the Western world.

Notes

1.

2. Rubus spectabilis is a kind of salmon-colored raspberry. Rubus chamaemorus is smaller and amber colored.

References

DiaTech test shows improved results for breast cancer patients. Businesswire.com. Dec. 10, 2012.

Carrière GM, Tjepkema M, Pennock J, Goedhuis N. Cancer patterns in Inuit Nunangat: 1998-2007. Int J Circumpolar Health. 2012;71:18581.

Kuhnlein HV, Turner NJ. Traditional Plant Foods of Canadian Indigenous Peoples. Taylor & Francis; 1991

Kumar S, Meuter A, Thapa P, et al. Metformin intake is associated with better survival in ovarian cancer: A case-control study. Cancer. 2012 December 9.

Stefansson V. Cancer: Disease of Civilization? Hill & Wang; 1960.

Stratton MR. Exploring the genomes of cancer cells: progress and promise. Science. 2011;331(6024):1553–1558.

©2013 by Ralph W. Moss

Ralph W. Moss, PhD, is the author of 12 books on cancer-related topics. The former science writer at Memorial Sloan-Kettering Cancer Center, for 35 years Moss has investigated the validity of many cancer treatments. He currently directs the Moss Reports, a library of reports for patients on over 200 different cancer diagnoses.