4 June 2019

Encouraging news for patients with metastatic estrogen receptor-positive (ER+), Her2/neu negative breast cancer was presented at the 2019 American Society of Clinical Oncology annual meeting, and published in the New England Journal of Medicine.

The MONALEESA-7 Phase III trial evaluated the use of ribociclib in combination with endocrine therapy. Patients who received ribociclib and endocrine therapy were found to have improved overall survival rates compared to those who received endocrine therapy alone. Prior studies demonstrated improved progression free survival, but this was the first demonstration of an improvement in overall survival. Patients enrolled in this study were pre- or peri-menopausal.

Ribociclib is an oral medication belonging to the CDK 4/6 inhibitor class of targeted agents. The CDK 4/6 pathway is important for cell division. CDK 4/6 inhibitors block progression through the normal cell cycle, so cancer cells are “arrested” in a resting phase and cannot divide. This study found that at 42 months, patients treated with ribociclib had a 70% overall survival rate, compared to 46% for the patients who received endocrine therapy alone. In absolute numbers, there were 26 fewer deaths (83 or 337 versus 109 of 335) in the treatment group. Because patients who develop metastatic breast cancer after a diagnosis of early-stage disease are not re-staged, it is not possible to determine with certainty how many patients this medication may be appropriate for. Approximately 40,000 women and 500 men die from metastatic breast cancer every year. ER+ is the most common breast cancer subtype.

Prior studies have evaluated a similar drug, palbociclib, which has been approved for use in women and men with metastatic breast cancer. There are ongoing studies evaluating all 3 of the “ciclib” agents to get a better sense of whether the results will be similar across all patient populations or if a particular drug will be better for a particular subset of patients. All 3 agents are oral (pills). While side effects may be an issue for some patients, these medications are much better tolerated compared to traditional chemotherapy. Unfortunately, cost and insurance coverage may be an issue in some situations.

In addition, I do think that it is important to point out that in the current study, the majority of patients (67% in the ribociclib arm and 73% in the endocrine therapy alone arm) went on to receive other therapy – meaning that the disease progressed. We are still a long way from a “cure” despite improvements in overall survival, and we’re a long way from single-agent therapy in patients with metastatic breast cancer. Patients with metastatic breast cancer are still expected to need more than one, and in some cases multiple, agents over time as the cancer finds ways to mutate and continue to grow. The findings of this study are a step in the right direction, but much more research is needed.

Additional Information:
NBC News – Breast Cancer Treatment Shows Hope for Younger Women

15 April 2018

Press coverage of a study recently published in the journal Science Translational Medicine has raised a lot of eyebrows and may be causing unnecessary worry in patients. The headline in USA Today noted “Healing process after breast cancer surgery may trigger cancer to spread, study says.”

Not mentioned in the headline: the study was performed in mice. Mice were injected with breast cancer cells, developed tumors, and then underwent a surgical procedure to implant a small sponge, I presume similar to the surgical gauze that is used in the operating room. Note – the mice did not have traditional breast cancer surgery. The study found that the mice that underwent the surgical procedure had a higher rate of developing metastatic breast cancer – spread to other organs of the body. They also found that when mice received anti-inflammatory agents (meloxicam – brand name Mobic – was used in the study), they had a lower rate of developing metastatic disease.

It is well known that surgery can cause an inflammatory response and alteration in immune system function.. It is not entirely clear what that means for the average patient undergoing breast cancer surgery, and we certainly do not see metastatic disease develop in the majority of patients treated with surgery. If inadvertently left behind in a surgical wound (a very rare event), surgical gauze causes significant swelling, pain, inflammation and often infection – not at all similar to the healing process from lumpectomy or mastectomy. We cannot make assumptions from this mouse study if the use of anti-inflammatory agents after surgery would be helpful in human patients.

The take-home point for me is from my quote in the Stat News coverage: “I do not know if this mimics the potential effect of a lumpectomy or mastectomy, but the inflammatory response to an implanted foreign body would be expected to be quite robust,” said UCLA’s Dr. Deanna Attai, a past president of the American Society of Breast Surgeons. That inflammation, not surgery, might be awakening dormant cancer cells. Nevertheless, she said, “this study and the handful of others like it certainly are interesting and warrant further study.”

Until we have more information, and studies in humans with breast cancer, breast cancer surgery remains an important component of treatment.

Health News Review coverage: A breast cancer study in mice gets big headlines, setting up potential for patient “disaster”, experts say

13 October 2016

The 13th of October is designated for metastatic breast cancer awareness. Metastatic, or Stage IV breast cancer, is when the cancer has spread outside of the breast or underarm lymph nodes. The most common sites of spread are the bones, liver, lung and brain.  Later stage of disease at the time of diagnosis is a risk factor, as is aggressive tumor biology. However, anyone who has been treated for breast cancer has the potential to develop metastatic disease. Metastatic disease can develop at any point after treatment – even many (15-20) years later. Approximately 6% of newly diagnosed breast cancer patients have metastatic disease at the time of diagnosis, known as “de novo” metastatic disease.

The overwhelming majority of the roughly 40,000 women and 500 men who die from breast cancer every year in the United States die from metastatic breast cancer. Patients who develop metastatic disease are on some form of treatment (chemotherapy, hormonal therapy, targeted agents, or a combination of medications) for life. Radiation therapy and surgery may also be used as part of treatment. In patients with metastatic disease, the focus shifts from potential cure of cancer to controlling areas of cancer growth and managing side effects related to treatment and disease progression. Treatments have improved considerably and many women and men with metastatic breast cancer are living longer than ever, but there is no cure.

During Breast Cancer Awareness Month, and all year, it is important to remember that early detection does not prevent spread. More aggressive surgery does not prevent spread. Metastatic cancer cells may be present before the tumor in the breast is even detected. Take a few minutes to become educated about the breast cancer that kills, and consider supporting research that is trying to find answers.

For more information:

10/13/2019 NPR Interview
Metastatic breast cancer information from
Metastatic Breast Cancer Network
Metastatic Breast Cancer Alliance

Updated 13 October 2019

25 August 2016

Patients with metastatic (Stage IV) breast cancer often undergo frequent blood tests and scans to monitor for disease progression. But is there such a thing as too much testing?

A study recently published in the Journal of the American Society of Clinical Oncology evaluated the use of blood tests (tumor markers) and body imaging scans (such as PET, CT, or bone scans). The Medicare-SEER database was used to identify women diagnosed with metastatic breast cancer from 2002-2011, and billing codes were then assessed to determine test utilization. Among 2460 eligible patients, 36.7% were “extreme users” of disease monitoring tests, defined as greater than 12 blood tests and/or 4 body imaging scans in a 12 month period. Medical costs were 59.2% higher in these patients.

Metastatic breast cancer is not curable. Patients with Stage IV breast cancer often are treated with some form of chemotherapy, hormonal therapy, or targeted therapy for life. The location and amount of tumor in the body are monitored using blood tests and body imaging, and treatments are adjusted if the disease progresses. How much monitoring is appropriate varies depending on the individual situation and whether or not a patient is participating in a clinical trial (some trials have specific requirements for testing). However, the authors of an accompanying editorial note that no clinical trial requires monthly blood tests or body imaging more than four times per year.

Intuitively, it would seem that the sooner progression is identified and treatment initiated (or changed), the better the prognosis. However, that is not yet the case. As novel treatments are discovered, this may change over time. But for now, more testing only adds to higher costs. As Dr. Leonard Lichtenfeld, the Deputy Chief Medical Officer of the American Cancer Society noted in his blog post: “No one likes to think of costs when it comes to medical care and especially when saving lives. But while a lab test or an imaging study may not make a difference to our care or the outcome of our illness it certainly does make a difference to our pocketbook. And even worse, it may give us a false sense of comfort when it doesn’t accurately reflect a change in our disease, or send us down another perhaps more toxic path of treatment when it wouldn’t make a difference to do so.”

1 March 2013

A study published in JAMA found that there is an increase in the incidence of young women (age 25-39) diagnosed with metastatic breast cancer. Metastatic breast cancer means that the cancer has already spread outside of the breast, most commonly to the lungs, liver, bone, and brain. Metastatic breast cancer is not curable, although newer treatments have improved the survival rates.

This study evaluated the SEER Database from 1973-2009. They found that while the incidence of breast cancer in young women is low, young women are more likely to have metastatic disease when first diagnosed. One criticism of the study is that we did not have the ability to detect metastatic disease in the 1970’s like we do today. So a woman diagnosed in the 1970’s might have been thought to have earlier stage disease, when in reality the cancer was already present in other areas of the body. Today, we are more likely to use a combination of blood tests and imaging scans to get better idea of the cancer stage – metastatic disease is considered Stage IV.

The following interview discussed some of the limitations of the study, as well as recommendations for young women. All women should be aware of their breasts and their bodies. While breast cancer is not common in young women, it certainly does occur. Any changes should be reported to your physician.

The Young Survival Coalition is an excellent resource and support organization for young men and women diagnosed with breast cancer, as well as their caregivers and support team.