UPDATED // A biomedical researcher with an unusually virulent form of breast cancer has taken an extraordinary step to "immortalize" her cancer cells.
Kimberly L. Koss, PhD, 57, skipped standard preoperative chemotherapy in an effort to culture pure versions of the cells removed after her mastectomy.
Chemotherapy would have damaged the cancer cells and made them less likely to live on in lab cultures, which is a rare scientific achievement. But chemotherapy also might have improved Dr. Koss's outcome.
"She is very brave and self-sacrificing," Keith Jones, PhD, who is leading the research team culturing the cells, said in a press statement. He is chair of the Department of Molecular Pharmacology and Therapeutics at the Loyola University Chicago Stritch School of Medicine.
"I think we can unlock the secrets of these deadly cells," said Dr. Koss in the statement. "I have a daughter and 3 granddaughters. I hope they never get this disease. But if they do, new treatments could be their salvation, as well as the salvation of many other women."
Dr. Koss also explained that her original biopsied cancer cells were unusable for the culturing, which necessitated her skipping chemo. "No 'living' cells were preserved in pathology and none were preserved by snap freezing...so no culture was possible from the biopsies," she told Medscape Medical News. Furthermore, undergoing a second needle biopsy to extract cancer cells for culturing was not considered because a large quantity of tissue was needed for the project's total lab work, which includes oncogene analyses, and was obtained from the mastectomy.
Dr. Koss, who recently retired from the University of Cincinnati, where Dr. Jones worked before moving to Chicago, has an especially aggressive case of triple-negative disease, which is notoriously difficult to treat, even in less severe cases.
Triple-negative tumors test negative for estrogen, progesterone, and HER2 receptors, and thus are not targetable with standard therapies such as trastuzumab (Herceptin, Roche) and tamoxifen.
Ironically, the very aggressiveness that threatens Dr. Koss's life also makes her cells good candidates for proliferation in cell cultures.
"Dr. Koss's tumor is highly invasive and measured abnormally high on a clinical index of growth — 3 times that of a tumor considered highly aggressive," Dr. Jones explained in an email to Medscape Medical News.
"This means that her cells undergo cell division rapidly. This is a characteristic of cancer cells that have been successfully grown in culture in the past."
Most cancer cells are not as aggressive as Dr. Koss's, and thus cannot continue to reproduce outside the body in the less hospitable host of a lab culture. In fact, even when a cancer is aggressive, a subsequent immortal cell line is "highly unusual," Dr. Jones said.
Cancer cell lines have been used for decades in research, but were little known outside the esoteric domains of laboratories until a book about them became a bestseller. The Immortal Life of Henrietta Lacks by Rebecca Skloot, published in 2010, described the genesis, long life, and wide use of the now famous HeLa cell line.
Dr. Koss's breast cancer cells are akin in their potency to Lack's cervical cancer cells, Dr. Jones reported.
"Measurements of growth of HeLa cells in culture, though hard to directly compare to the clinical measurement, are in the same ballpark [as Dr. Koss's], and they have been in culture since the 1950s. Therefore, our chances to achieve this are high," Dr. Jones told Medscape Medical News.
But there is a big difference between Henrietta Lacks and Dr. Koss.
Lacks' remarkable cellular progeny were cultured and reproduced without her knowledge or consent, and were subsequently exploited by medical institutions and companies. However, it has been pointed out that patient consent was not commonplace at the time.
One of the consequences of the publicity generated by the book was a "unique agreement" reached in 2013 between the National Institutes of Health and the Lacks family.
Any successful cell line from Dr. Koss would not be exploitive or without consent. It was her idea.
Dr. Koss suggested entrusting her tumor cells to Dr. Jones when he visited his ex-colleague and collaborator in an oncology critical care unit.
"Dr. Jones is absolutely the smartest researcher I've ever met," said Dr. Koss. "I trust him on every level."
Dr. Jones and Dr. Koss control the rights to her cells. Currently, there are no plans to commercialize them, he said.
In the next 6 months or so, Dr. Jones and his Loyola team should know if the cells can live on in lab cultures.
In the meantime, Dr. Koss is scheduled to undergo postoperative or adjuvant chemotherapy.
The impact of her skipping standard neoadjuvant chemotherapy is not known precisely. However, a meta-analysis from German researchers demonstrated that long-term survival is better in breast cancer patients who attain a pathologic complete response (pCR) after neoadjuvant chemotherapy than in those who do not, and that patients with triple-negative disease are among the greatest beneficiaries (Cancer Res. 2012;72[24 Suppl]:S1-11). At least 1 other study has shown that for patients with triple-negative disease, some regimens are better than others for achieving a pCR. Whether or not neoadjuvant chemotherapy is eventually proven in a phase 3 trial to prolong survival in patients with triple-negative disease remains to be seen, said Dr. Jones. "Studies are ongoing," he noted.
There is an outstanding need for more immortal breast cancer cell lines, said Dr. Jones.
"There have been other cell lines derived from breast cancer patients, including some from triple-negative patients. However, most of these were derived 30 to 40 years ago, and not directly from tumors but from metastases and from pleural effusions," he explained.
Also, there is a boatload of problems with the various triple-negative breast cancer cells lines.
"Many were not triple negative in situ (the tumors were not triple negative but the cells later were found to be), and some have recently been found to be contaminated with other types of cancer cells," said Dr. Jones.
In one case, a triple-negative cell line was found to be contaminated with melanoma cells. More than 200 scientific publications that examined this line are now considered "much less useful" as a result, he noted.
Cancer cell lines are valuable because they facilitate basic research and set the stage for clinical advancements, Dr. Jones said.
In the case of triple-negative breast cancer, basic questions are unanswered, such as the source of the cells' abnormality, rapid growth, and invasiveness.
The development of cancer cell lines has entered a new era, suggested Dr. Jones. And Dr. Koss's contribution takes advantage of that.
He explained that technologic advancements now allow for complete genomic and gene-expression analysis of a tumor and for protein marker analysis. Researchers "can therefore repeat these analyses in the cell lines to confirm their gene structure and expression," he said.
The result is better scientific evidence.
"This will allow us to confirm that the cell lines used for study reflect the actual tumor tissue the way it was in the body, before it was extracted," he said. "This is an opportunity we did not have before."
Loyola has established the Dr. Kimberly Koss Breast Cancer Research Initiative Fund to support such research. Dr. Koss is also fundraising for the research on a crowd-sourcing Web site.
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Cite this: Researcher Skips Treatment to 'Immortalize' Her Own Cancer - Medscape - Jul 29, 2014.