6 advances in breast cancer diagnosis and treatment →

BY CYNTHIA DEMARCO

December 05, 2019

Breast cancer remains one of the two most-common types of cancer in the world, according to the World Health Organization. It’s the fifth-leading cause of cancer-related deaths annually. And more than 265,000 people will be diagnosed with it in the United States alone, during any given year.

But there is reason for hope. Research has yielded a number of exciting developments in breast cancer diagnosis and treatment that will improve the lives of breast cancer patients for years to come. We spoke with our Senthil Damodaran, M.D., Ph.D., Jennifer Litton, M.D., and Anthony Lucci, M.D.,to learn more.

1. Node preservation reduces lymphedema cases

Axillary lymph nodes used to be removed from the armpit routinely during breast cancer surgery to test for metastasis. This caused chronic pain, numbness and lymphedema in about 1 in 5 patients. But studies have shown that many of those nodes can be preserved — without compromising long-term survival rates.

Sentinel node mapping lets surgeons identify which lymph nodes are most likely to be affected by a tumor. Targeted axillary dissection allows surgeons to potentially preserve nodes that once tested positive for cancer, but reverted to negative status after chemotherapy or another treatment. In both cases, if tests come back negative for cancer on the first few nodes taken out, the remaining nodes can be left alone. That means fewer complications, and fewer side effects for our breast cancer patients.

“About 15-20% of patients developed lymphedema when we were still routinely taking all the nodes out,” says Lucci, a surgical oncologist who specializes in breast cancer. “But when sentinel node mapping is done, and the rest of the nodes are left in place, that figure drops to 5%. And the chance of a recurrence in the axilla is quite small using this strategy. So, this is a huge deal. We’ve really been able to improve patients’ quality of life by dialing back our aggressiveness on routine lymph node removal.”

2. Genomic testing minimizes chemotherapy exposure

For years, many patients also got chemotherapy as a part of their breast cancer treatment. But a July 2018 study in the New England Journal of Medicine showed that chemotherapy wouldn’t benefit up to 85% of patients over age 50 whose breast cancer was HR+, HER- and had not spread to any lymph nodes.

The study involved a genomic assay (or OncotypeDX test) that looked at the expression of 21 different genes in a patient’s primary tumor. A tumor’s gene expression pattern shows whether or not it will be responsive to chemotherapy, or whether endocrine therapy alone (such as tamoxifen) would be a better choice. The study showed that patients scoring in the low-to-mid-risk range could safely skip chemotherapy, avoiding the hair loss, neuropathy, weight lossand other side effects that often come with it.

“Before that study, we didn’t know if it was safe to omit chemotherapy,” says Lucci. “Now, we know we can get the same overall outcome by doing less. So, we’re minimizing overtreatment. And it has totally changed how we practice medicine.”

3. Better identification of hereditary cancer syndromes

A number of genetic mutations — such as BRCA1 and BRCA2 — are already known to increase a person’s risk of developing certain cancers, including breast cancer. But now, next-generation gene sequencing techniques are helping researchers identify other hereditary cancer syndromes that can put people at risk.

“We always knew there were certain families with strong histories of cancer,” says Litton, a medical oncologist who specializes in breast cancer genetics. “But by analyzing blood and saliva, we can reach out to other family members earlier – both to provide preventive care through enhanced screenings and to identify existing cancers.”

4. An oral option for targeted therapy

Until recently, PARP inhibitors were used primarily to treat ovarian cancer. They work by preventing damaged cancer cells with specific genetic mutations from repairing themselves. Today, this targeted therapy is being used to treat breast cancer successfully, too.

“DNA has multiple ways to repair itself,” explains Litton. “So, when someone has a genetic mutation that closes one pathway, their DNA uses another one instead. PARP inhibitors block those escape routes, so cancer cells can’t grow and divide.”

Breast cancer is linked to fewer mutations than ovarian cancers, Litton notes, but PARP inhibitors can still exploit them. Two Phase III clinical trials are currently underway comparing PARP inhibitors to standard-of-care chemotherapy. The OlympiAD trial evaluated olaparib and the EMBRACA trial, led by Litton, evaluated talazoparib. Both trials showed improvements in progression-free survival for patients with an inherited BRCA gene mutation and metastatic breast cancer. Both studies also showed overall improvements in quality of life in patients who received these oral drugs, as opposed to those patients who received chemotherapy. 

“It’s fantastic that patients now have an oral option in this class of drugs,” says Litton. “We’re exploring some very promising combinations in clinical trials that try to create a BRCA-like environment for PARP inhibitors to work, even in women who don’t have the targeted mutations. Early results indicate that some patients will still have a complete response: meaning no cancer can be found in their breasts at the time of surgery.”

5. New drug combination makes estrogen-blocking agents more effective

Patients with HR+ — or hormone receptor-positive — breast cancers are often prescribed estrogen-reducing agents such as letrozole and anastrozole to starve the tumors. Now, studies show that those patients do even better when hormone therapy is combined with CDK4/6 inhibitors, which prevent cancer cells from dividing.

“Three different CDK4/6 inhibitors have been approved by the U.S. Food & Drug Administration: abemaciclib, palbociclib and ribociclib,” says Damodaran, a medical oncologist who specializes in breast cancer. “When combined with hormone therapy, all three CDK4/6 inhibitors have shown immense improvement in progression-free survival in patients with stage IV breast cancer. So, this has become the standard of care in nearly all metastatic HR+ breast cancer patients for first-line treatment. It’s a big change in how we treat breast cancer.”

6. The next generation of monoclonal antibodies

Trastuzimab (Herceptin) is a monoclonal antibody that has been used to treat HER2+ breast cancer patients since the 1990s. It works by targeting the HER2 receptor, preventing cancer growth. Some breast cancers express too much HER2 protein, triggering the cells to multiply very rapidly.

Other monoclonal antibodies (such as pertruzimab/Perjeta) have since been developed. Today, this targeted therapy has gotten even more advanced. T-DM1 (Kadycla), an antibody-drug combination, has been approved for use in the treatment of HER2+ breast cancers. Antibody-drug combinations work like a “smart bomb,” delivering chemotherapy directly to cancer cells by attaching to their HER2+ receptors.

“Targeted therapies have transformed our approach to HER2+ breast cancers, and offer an opportunity to cure stage IV breast cancer in certain patients,” says Damodaran. “So, monoclonal antibodies have been a big game-changer.”

Meet breast surgical oncologist Anthony Lucci, M.D. →

Click to view personal interview with Dr. Lucci.

EXCITING NEWS FROM DR. LUCCI

NEWS from Dr. Lucci’s latest research - We are now assessing blood samples from our high-risk breast cancer patients- such as triple-negative or inflammatory breast cancer, or locally-advanced patients- to look for mutations within the blood- also known as a "liquid biopsy"- to identify those mutations that can be used as targets for new drug therapy. One example would be to look for mutations in PIK3CA and adding a drug known to act against this. This is the way of the future!  I believe that in the near future we will be able to identify certain mutations that will guide our therapy choices, allowing us to choose the drug most likely to kill the tumor. This will be a big advance, and its coming in the near future. in case we think its far off, recently such a mutation was found in lung cancer patients, and now such a liquid biopsy is used in the clinic to help guide lung cancer treatment.  We are hopeful that breast cancer is not far behind. 

OTHER important news from Dr. Lucci - Recent research (not on CTC research but on IBC) shows we can achieve local control rates equal time non IBC - not done before. We are combining this with our CTC blood data:

The ASCOT Post

May 25, 2017

By Caroline Helwick

"Triple‑Modality Therapy Achieves Good Control in Inflammatory Breast Cancer"

‘Shift in Thinking

Anthony Lucci, MD, Professor of Surgery at MD Anderson Cancer Center and the study’s senior author, emphasized the relevance of their findings. “We frequently see patients with inflammatory breast carcinoma who are being told, ‘There is no reason to remove the primary,’ or ‘You are not a candidate for mastectomy.’ In our study, using an aggressive approach to resection of the primary, we were successful 99% of the time in achieving negative margins by performing a modified radical mastectomy after neoadjuvant chemotherapy,” he said in an interview.

“The patients then completed their trimodal therapy by undergoing postmastectomy radiation therapy specific to inflammatory breast carcinoma, resulting in local recurrence rates that were no different from patients with other forms of breast cancer,” Dr. -Lucci said. “This represents a significant improvement in previously reported local recurrence rates in this disease.”

Dr. Rosso added that the surgeons closely examine the pretreatment photos to better appreciate the degree of diffuse skin involvement. “We don’t spare much skin. We take everything off the muscle and include the muscle when it is involved,” she said. In most cases, primary wound closure is possible; in about 15% of cases, the wound requires a tissue flap by a plastic surgeon.

“We feel this represents a shift in thinking regarding the management of patients with inflammatory breast cancer,” Dr. Lucci offered. “That is, it debunks the outdated thinking that ‘There is no good reason to aggressively resect all of the local disease to negative margins in patients with inflammatory breast cancer, since the thinking is that they might have a distant recurrence, and local control is not that important.’”

To view full article:

http://www.ascopost.com/issues/may-25-2017/triple-modality-therapy-achieves-good-control-in-inflammatory-breast-cancer/

Update on Dr. Lucci's Research and Our Fundraising Efforts

Since the partnering of Dr. Anthony Lucci's Breast Cancer Research at The University of Texas MD AndersonCancer center and the Emma Jacobs Breast Cancer Foundation, we are now knocking at the door of successfully raising close to $200,000!!! 
 
We are thrilled to report that our November 5, 2015 EJBCF Color Me Pink event raised over $40,000! That combined with past years fundraising by the foundation, we can now proudly announce that we have donated just shy of $200,000 to Dr. Lucci’s brilliant endeavor for breast cancer research.
 
Dr. Lucci would like to share this latest news about his research:
 

I would like to thank you for your generous support of my micrometastases research at The University of Texas MD Anderson Cancer Center. We could not have realized our exceptional advancements this year if not for your generosity and devotion to our research program. The last few months of 2015 were very eventful, and we are excited about upcoming 2016 projects!
 
As some of you know, in late 2015 we published paper in the Journal of the National Cancer Institute describing the role CTCs play in disease progression in stage III inflammatory breast cancer patients. This is important since it could be used to identify those patients at higher risk for relapse, thus enabling us to intervene before a relapse occurs.  We already have a paper published in 2016!  It is a study we spearheaded with our European colleagues, Pooled Analysis of the Prognostic Relevance of Circulating Tumor Cells in Primary Breast Cancer, which has been published in the journal Clinical Cancer Research.  This report, which included more than 3100 stage I-III breast cancer patients, is a multi-institutional study (Germany, France, Netherlands, and our group) showing that one or more circulating tumor cell per tube of blood predicts relapse and death. This is a groundbreaking report because it demonstrates that as few as one circulating tumor cell can be reliably identified amongst many different clinical laboratories.  More importantly, it clearly demonstrates that circulating tumor cell assessment is a valuable tool for predicting relapse in breast cancer patients, even early stage patients with T1/T2 tumors.
 
We can now characterize CTCs from stage I-III patients so that targeted therapies can be developed to kill these harmful cells. We now have the ability to isolate single CTCs, amplify the DNA sequences within each CTC, and perform molecular analyses on individual cells to determine if CTCs harbor mutations that promote metastasis. Simultaneously, we are identifying additional factors that tumor cells shed into the bloodstream that can be used to develop new individualized treatments for patients. We have analyzed blood from 30 stage III triple negative breast cancer patients for tumor-derived DNA (DNA released by tumor cells into the blood.  Another tool tumor cells use to promote cancer spread are exosomes.  Exosomes are like “microscopic balloons” that cancer cells release into the bloodstream.  These balloons are filled with proteins and RNA that can travel in the blood to distant sites, such as the bone, lung, and brain. The exosomes actually enter the cells at these distant sites and “prime them” so that the cancer cells can establish metastases later.  We have analyzed blood from several breast cancer patients and compared exosome proteins in patients who have recurred and those who remain disease free. Together, these combined results can be used as “liquid biopsies” that will facilitate the development of individualized therapies to eradicate CTCs, and specific DNA mutations and proteins in the blood that can be used to predict disease progression while concurrently identifying new targets for drug development.
 
Most importantly, none of this work would be possible without the generosity of each of you in helping us have the resources available to reach our goal of eliminating cancer. Thanks again for being a part of our team!     

This is an electron microscopy picture of an exosome cross section Isolated from a stage II breast cancer patient’s blood.

Recent Developments of Dr. Anthony Lucci

Over the past year we have made some important advancements in our knowledge about how breast cancer spreads by depositing cells into the bloodstream. And we could not have realized these advancements if not for the incredible generosity of our donors, including the Emma Jacobs Breast Cancer Foundation.

As a result of your participation, we have identified, characterized and validated the importance of harmful circulating cancer cells (CTCs) and disseminated cancer cells (DTCs) in operable breast cancer patients.  Last year we published a first-of-its-kind paper in the Lancet Oncology demonstrating the clear prognostic significance of CTCs found in early-stage breast cancer patients. We have recently submitted a paper demonstrating the prognostic significance of CTCs in triple negative breast cancer patients to the journal Cancer.  We are also developing methodologies to characterize CTCs and DTCs so that targeted therapies can be developed to kill these harmful cells.

In 2013 we published a paper in Cancer Medicine demonstrating that most CTCs and DTCs express a protein called HER2, even when it is not expressed by a patient's primary tumor. However, these patients are not offered standard anti-HER2 medications (such as Herceptin) that could kill these DTCs and CTCs because current cancer treatment decisions are based solely upon primary tumor characteristics.  Our paper highlights the need for trials examining therapies directed against targets expressed by both primary tumor and CTCs/DTCs to improve outcomes for breast cancer patients with CTCs and/or DTCs.  We have also recently submitted a paper showing the importance of CTCs in triple-negative breast cancer patients.  This report is particularly important as triple-negative patients have only limited therapy options. Our next step is to characterize genetic mutations in the CTCs in these patients so that new, targeted therapies can be identified to improve outcomes in triple-negative breast cancer.

If any of the readers are interested, we would be happy to forward copies of the scientific manuscripts we have published.  We again want to stress that many of these projects were funded through your generous donations, so we are happy to send copies of our results to those who have an interest in knowing more.  We will continue to study and identify novel ways to prevent breast cancer metastasis and improve survival for all patients with cancer. These studies would not be possible without the generous support of people like you.  We truly appreciate all you do for us.

If we can stop cancer metastasis, we can save lives.

This is the goal of Dr. Anthony Lucci at MD Anderson Cancer Center. 

Since I last wrote you, Dr. Lucci has made some incredible advances in his breast cancer metastasis research.  He has found that cancer cells can be identified in the blood and bone marrow of 25 percent of patients with early stage breast cancer.  More tragically, he has also found cancer cells in the bone marrow of 25 percent of breast cancer patients who have undergone chemotherapy.

But there is hope.  Dr. Lucci’s lab is uncovering the reasons that some chemotherapies do not work against metastasis.  One reason: primary tumors and metastasized cells have different genetic make-ups.   Therefore, a therapy that works on the primary tumor might be not work against metastasis.  Another reason: standard chemotherapy regimens work by killing cells, both cancerous and healthy, as they are dividing.  However, Dr. Lucci has found that metastasized cells in the bone marrow lie dormant and divide slowly, thereby rendering many chemotherapies ineffective.

Thanks to philanthropy and your help, hope is on the horizon.  Dr. Lucci published the first report showing that a specific enzyme present in the primary tumor is the best predictor of whether cancer cells will metastasize to bone marrow.  This critical discovery allows researchers to develop therapies that target the enzyme to prevent metastasis.  Dr. Lucci’s laboratory has already confirmed that the enzyme inhibitor prevents metastasis in mouse models, and plans are underway to develop a clinical trial for use in humans.

Please consider supporting Dr. Lucci and his research. You are making a difference in the lives of millions of breast cancer patients and survivors.

MD Anderson’s initial goal of $1 million is 94% completed with $38,000 to go.  Which is fantastic.  To move to the next level, Dr. Lucci and his group are looking to raise another $1.5 million (for a total of $2.5 million) to accomplish his long-term research goals for breast metastases. 

Any help that we can give I know will be appreciated.

Thanks for your support!