Of Mice and Mammaries, Part 1: There’s something in the milk

In light of Breast Cancer Awareness Month, Justin Varholick traces how mice have helped breast cancer research over the past century. In the first post this 4-part series, we look at advances made from 1854 to 1940, including the understanding of the role of breast milk in causing certain types of tumors. 

Image credit: Jackson Labs

Breast cancer is one of the most serious forms of cancer facing women. Each year, over 300,000 women in the U.S. will be diagnosed with breast cancer, and it is estimated that 40,610 women will die from it in 2017 alone. Thankfully, death rates from breast cancer have dropped almost 40% from 1989 to 2015, and there are over 3.1 million breast cancer survivors living in the U.S. today.

Breast cancer grows and spreads through many stages, and can start in different parts of the breast. Some types of breast cancer cause lumps, others form no lumps. Some forms of it spread very quickly throughout the body, while others spread more slowly. Because breast cancer spreads and forms at different rates and in different areas of the breast, treating it is no easy task. It is also unlikely that we will one day have a “cure” for breast cancer — one size cannot fit all.

Despite the complicated nature of breast cancer, scientists feel a responsibility to understand it as much as possible in efforts to find new treatment methods and forms of a cure. Over the years they have made great strides in their research by studying mice. These mice serve as an essential step between early research on mammary cells and clinical trials in humans.

Over the course of this month, I will highlight some of the key findings scientists have discovered about breast cancer through their studies in mice.

1854 to 1903 — The first mouse mammary tumors

The first discovery of a mammary tumor in a mouse was in 1854. In these early days, scientists were able to find tumors spontaneously growing in female mice kept as pets and in the wild. Although they were able to detect and describe these tumors, it was difficult to understand where they came from, and how they grew and possibly spread or metastasized.

Thankfully in 1903, Dr. Carl Jensen developed a line of “high tumor” mice that readily grew mammary tumors, which could be easily transplanted to other mice. By transplanting the tumors in other mice, they could measure how and where the tumors spread, in otherwise healthy mice.

During this time in history, 1.2* women per 1,000 died from breast cancer in the U.S. Today it is around 0.13 women per 1,000. (*at this time we only had reports on the number of white women in the U.S.).

1933 to 1940 — There’s something in the milk

After bringing mice into the laboratory and thoroughly studying their biology, a great discovery was made — there was something in the milk. This discovery was made by Scientists at Jackson Laboratories, in Bar Harbor, Maine. They bred “high tumor” mice with “low tumor”* mice and found that offspring were more likely to get mammary tumors if they had a “high tumor” mother. Although some scientists were able to replicate this finding in other labs, very few were convinced there was something in the milk — they believed it was passed down through the genes. (* an extremely low number of “low tumor” mice were found with mammary tumors; because of this scientists could not call them “no tumor” mice.)

To answer whether there was either something in the genes or the milk, Dr. John J. Bittner did a more complex study 3 years later. In this key study, Bittner cross-fostered mouse pups from “high tumor” and “low tumor” mice to opposite mothers (see diagram). This method allowed him to determine whether the parent’s genes or the foster mother’s milk lead to mammary tumors. If it was the genes then “high tumor” offspring would have tumors whether they had “high tumor” or “low tumor” foster parents. If it was the milk then any offspring nursed by “high tumor” mothers would get tumors.

Through this experiment, Bittner found out that milk was a key factor. “Low tumor” pups cross-fostered to “high tumor” mothers had many mammary tumors, while “high tumor” pups cross-fostered to “low tumor” mothers had very few tumors. “High tumor” pups nursed by their own mothers, however, had the highest rates of tumor growth. It didn’t always matter who the parents were, it also mattered who nursed the pups. This verified that indeed there was something in the milk. This something was labeled as the Mouse Mammary Tumor Virus (MMTV).

Dr. Bittner was often heard stating that he only studied the milk because nobody else wanted it — they all wanted to study the genes.

To be continued…

Tune in next week to read what we learned about the milk virus, MMTV, and what we did with this new power!

Justin Varholick

References

  1. Cardiff R, Kenney N. (2011). A compendium of the mouse mammary tumor biologist: From the initial observations in the house mouse to the development of genetically engineered mice. Cold Spring Harb Perspect Biol. 3(6).
  2. Holen I, Speirs V, Morrissey B, Blyth K. (2017). In vivo models in breast cancer research: progress, challenges and future directions. Dis Model Mech. 10(4).
  3. Tarone RE, Chu KC. (1992). Implications of birth cohort patterns in interpreting trends in breast cancer rates. J Natl Cancer Inst. 84(18).

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