Friday, January 6, 2012

Triple Negative What?

by Michael

I flew to Ottawa earlier this week for my Uncle John's funeral. He was 67, husband, father of four boys, grandfather of five, a retired diplomat, and one of the most complex and compassionate persons I've met.

On the plane ride home I was having a conversation with Kate's oncologist in my head. Triple negative breast cancer? What does that mean? It seems to mean that the available treatment options are "negative." Can't block the cancer with estrogen inhibitors, for example.

Incurable? I've spent a lot of time at Princess Margaret Hospital these past 16+ months. There are huge banners promoting a world without cancer. Believe!

I thought, A supposedly incurable breast cancer must be a medical researcher's wet dream. There are tens of millions of dollars being spent on cancer research. Someone must be looking at "triple negative."

What is that anyway?

So today I did what I have been avoiding. I went to Google and typed in triple negative breast cancer latest research. It turns out that the latest research is that there's no such thing as triple negative breast cancer. Just like there's no such thing as breast cancer. There are multiple diseases that produce tumors in the breast. Research (published in July 2011) has identified six sub-types of triple negative breast cancer.

There is also a Triple Negative Breast Cancer Foundation and a Guide to Understanding Triple Negative Breast Cancer.

And a potential treatment ... PARP inhibitors. (Though other research was less promising (May 2011.))

I'm going to paste below an article (from January 2011) from the website that gives the positive spin of this cutting edge experimental option:

PARP Inhibitor Shines in Triple-Negative Breast CA

Iniparib is one of several experimental medicines called PARP inhibitors. This small, early study suggests that iniparib can help treat metastatic triple-negative breast cancer.
Metastatic breast cancer is cancer that has spread to other parts of the body away from the breast, such as the bones or liver.
Triple-negative breast cancer is:
  • estrogen-receptor-negative
  • progesterone-receptor-negative
  • HER2-negative
Overall, about 15% to 20% of breast cancers are triple-negative. Triple-negative cancers are usually more aggressive, harder to treat, and more likely to come back (recur) than cancers that are hormone-receptor-positive and/or HER2-positive. Hormonal therapy and the targeted therapies Herceptin (chemical name: trastuzumab) and Tykerb (chemical name: lapatinib) usually don't work on triple-negative breast cancer.
The PARP (poly ADP-ribose polymerase) enzyme fixes DNA damage in cells, including DNA damage caused by chemotherapy medicines. Scientists developed PARP inhibitors based on the idea that a medicine that interferes with or inhibits the PARP enzyme might make it harder for cancer cells to fix damaged DNA. This would make the cancer more susceptible to chemotherapy and make it harder for cancer to become resistant to chemotherapy.
In this small, early study, 123 women diagnosed with metastatic triple-negative breast cancer were treated with the chemotherapy medicines Gemzar (chemical name: gemcitabine) and Paraplatin (chemical name: carboplatin). Half the women also got iniparib along with the chemotherapy regimen; the other half didn't.
Gemzar destroys cancer cells by acting as false building blocks in the cells' genes, causing the cells to die as they get ready to divide. Paraplatin weakens or destroys cancer cells by damaging the genetic material in the cells, and making it hard for cells to repair any genetic damage. Gemzar, Paraplatin, and iniparib are all given intravenously.
This study was an open-label study. This means that the women in the study and their doctors knew if they were getting iniparib or not. The women who didn't get iniparib didn't get a placebo (sugar solution) that looked like iniparib. Open-label studies aren't considered as objective as blinded studies (none of the participants or doctors know who is getting the experimental treatment and who isn't). Still, open-label studies are common when an experimental treatment is starting to be evaluated for benefits and safety in people.
More than half (56%) of the women who got iniparib had some response to treatment -- either the cancer went away (complete response), became smaller (partial response), or didn't grow for at least 6 months (stable disease) -- compared to 34% of the women who didn't get iniparib:
  • 52% of the women who got iniparib had a complete or partial response compared to 32% of the women who did not get iniparib
Women who got iniparib lived about 6 months without the cancer growing. Women who didn't get iniparib lived about 3.6 months without the cancer growing (progression-free survival).
Women who got iniparib lived about 12.3 months overall. Women who didn't get iniparib lived about 7.7 months overall (overall survival).
Nearly all the women eventually had the cancer grow while they were being treated, whether or not they got iniparib. This suggests that even though iniparib may boost the benefits of chemotherapy for a while, eventually the cancer becomes resistant to iniparib when it's used with chemotherapy.
Most inherited cases of breast cancer are associated with an abnormal BRCA1 or BRCA2 gene. Women who have one of these abnormal genes face up to an 85% risk of developing breast cancer by age 70. Their risk of ovarian cancer also is higher than average. Some experts think that PARP inhibitors such as iniparib may help treat women with an abnormal breast cancer gene. This may be because breast cancer cells in people with these abnormal genes already have a hard time repairing DNA damage from chemotherapy and PARP inhibitors boost the cancer cells' susceptibility to chemotherapy. Still, this study wasn't designed to look at these possibilities. The researchers didn't screen the women in the study for an abnormal breast cancer gene, though it's likely that some women did have one.
Some of the women had serious (grade 3 or grade 4) chemotherapy-related side effects, whether or not they were treated with iniparib. These side effects included: low white blood cell counts (neutropenia), low red blood cells counts (anemia), low platelet counts (blood cells that help with clotting), severe fatigue and loss of strength (called asthenia), and signs of liver effects (increase of a liver enzyme called alanine aminotransferase). Women who got iniparib were about 5% more likely to have severe side effects.
Other small, early studies have shown that some advanced-stage breast cancers -- including triple-negative breast cancers -- that have stopped responding to standard treatments will respond to chemotherapy combined with a PARP inhibitor.
If you're being treated for advanced-stage breast cancer, you and your doctor may be considering a number of options, especially if the cancer is triple-negative and/or has stopped responding to standard treatments. Treatment with an experimental regimen that includes a PARP inhibitor such as iniparib may be an option if you're willing to participate in a clinical trial. Ask your doctor if there are any clinical trials that might be a good fit for you and your unique situation. Visit the Clinical Trialspages for more information.

1 comment:

Kristine said...

Thank you Michael for sharing this. I'm so thankful that you are in Kate's life.