Breast Cancer Recurrence: New Breakthrough Could Decrease the Risk of Breast Cancer Returning
Scientists at The Institute of Cancer Research (ICR) in London have discovered why breast cancer cells that have spread to the lungs may ‘wake up’ many years after spreading, and forming secondary tumors, known as breast cancer recurrence.
The study, published in the journal Nature Cancer and funded by Breast Cancer Now, reveals the mechanism that sets off this breast cancer “time bomb” that leads to breast cancer recurrence, and proposes a potential method to defuse it.
The most common type (about 80%) of breast cancer is fueled by the hormone estrogen, known estrogen receptor positive (ER+) disease. Patients with ER+ disease have a significant risk of their cancer returning in another part of their body up to 30 years after their original diagnosis and treatment. Secondary, or metastatic breast cancer, refers to the spread of breast cancer cells from the breast to other parts of the body including the lungs, bones and liver. This is known as stage 4 disease. Although this can be treated and slowed down, it cannot be cured. This is because metastatic cancer cells eventually become resistant to the currently available hormone therapies and chemotherapies.
This new study performed in mice demonstrates how molecular changes in the lung that occur during normal aging may support the growth of these secondary tumors.
Cancer Cells “Reawaken” in Response to a Normal Protein
The Platelet Derived Growth Factor (PDGF) family of normal protein molecules helps damaged tissues heal and grow. The study found that a form of PDGF-C, a form of PDGF which is normally present in the lung, plays a key role in influencing whether rogue, inactive breast cancer cells stay asleep or ‘wake up.’
The study found that in young mice, dormant ER+ breast cancer cells in the lungs only produce a small amount of PDGF-C. This is enough for these cells to stay alive, but not enough to grow and spread. Older mice have more PDGF-C in their lung tissue which awakens the cancer cells and helps them grow. Furthermore, these awakened, stimulated cells produce more PDGF-C themselves which further increases growth.
Blocking PDGF-C Slows the Growth of ER+ Breast Cancer Cells
Dr. Frances Turrell, postdoctoral training fellow in the Division of Breast Cancer Research at ICR said: “Cancer cells can survive in distant organs for decades by hiding in a dormant state. We’ve discovered how aging lung tissue can trigger these cancer cells to ‘reawaken’ and develop into tumors and uncovered a potential strategy to ‘defuse’ these ‘time bombs’.
Drugs that block PDGF-C could potentially prevent these dormant ER+ cells from waking up and growing. These drugs could potentially even prevent metastasis from happening in the first place. One such drug that prevents cells from recognizing PDGF-C is Imatinib. Imatinib is a drug currently used to treat certain types of blood cancer like chronic myeloid leukemia. In this study, mice were treated with Imatinib before and after the lung mets had grown. In both groups, there was less cancer growth in the lungs.
These results suggest that Imatinib could one day be used to prevent breast cancer recurrence by slowing down or even stopping the growth of lung mets in women and men with ER+ disease. It could also potentially be used as a preventative treatment in patients with early-stage breast cancer and a high risk of recurrence.
While the results of this study are very exciting, unfortunately, we are still several years away from this treatment becoming clinically available. This study has so far only been performed in mice and more studies are needed to ensure the same results can be safely duplicated in humans.
Breast Cancer Pill Reduces Risk of Breast Cancer Recurrence
In a groundbreaking study, a drug called Lynparza (Olaparib) wa found to reduce the risk of breast cancer recurrence in BRCA gene mutation carriers. The pill, which is classed as a PARP inhibitor, was developed by AstraZeneca and Merck.
PARP inhibitors block the cancer cell’s ability to repair its own DNA. This means if a cancer cell is damaged by a treatment like chemotherapy or radiation, it will be unable to repair itself and will die.
New England Journal of Medicine Study
The clinical study, published in the New England Journal of Medicine, began in 2014 and enrolled a total of 1,836 women. All the study participants were carriers of a BRCA gene mutation and had a history of early stage HER2-negative breast cancers. All patients had undergone breast cancer surgery and chemotherapy and were also considered at high risk for breast cancer recurrence based on their tumor size or lymph node involvement.
Half of the study participants were given Lynparza daily for a year. The other half received a placebo. A little over two years after the beginning of treatment, the study found that the women taking Lynparza saw a 42% reduction in the risk of breast cancer recurrence or death. The study also reported that at 3 years after beginning treatment, 85.9% of Lynparza users were still living without evidence of a recurrence, compared to 77.1% of women who received the placebo.
As it stands today, AstraZeneca will be submitting the results of this study to regulators to request approval for use in early-stage breast cancer patients with a BRCA genetic mutation. Currently the drug is approved by the FDA to treat advanced-stage breast cancer in BRCA gene mutation carriers.
New Blood Test could predict Breast Cancer Recurrence and even prevent Surgery
While there is still much work to be done, detection and treatment of early stage breast cancer have improved tremendously over the last few years. Chemotherapy regimens have become increasingly effective, boosted by the emergence of immunotherapy, and often lead to a ‘pathological complete response’ when given before surgery (known as ‘neoadjuvant therapy’). A pathologic complete response means there is no identifiable tumor in the tissue that is resected by the lumpectomy or mastectomy.
However, there is currently no way to truly know which patients treated for early stage breast cancer enter remission and which ones actually have residual cancer cells in their system (in the absence of obvious metastatic disease).
A recent study published in Science Translational Medicine reported very encouraging news on a test called Targeted Digital Sequencing (or ‘TARDIS’) that could potentially help predict which patients are at high risk of breast cancer recurrence. TARDIS identifies DNA released by breast cancer cells into the bloodstream but is up to 100 times more sensitive than other liquid-biopsy tests currently available or in development.
This could be a huge step forward since TARDIS will potentially help doctors identify patients with early stage breast cancer who may still have residual cancer cells in their bodies after treatment that aren’t otherwise detectable by standard scans and follow-up monitoring.
It is also possible that the test could help remove the need for surgery altogether in women who experience a pathological complete response with neoadjuvant chemotherapy and are shown to have no residual breast cancer DNA in their bodies.
Very exciting news indeed! Read the full article here.
Does DIEP flap breast reconstruction increase the risk of breast cancer recurrence?
Patients choosing to undergo breast reconstruction are often concerned that their decision may increase their risk of breast cancer recurrence. A recent study published in the British Journal of Surgery looked at the risk of recurrence specifically after DIEP flap reconstruction.
The study compared 250 patients who had DIEP flap reconstruction between 1999 and 2013 with more than 700 control patients. Breast cancer recurrence was seen in over 19 percent of patients who had DIEP flap surgery and over 23 percent of patients in the control group. Interestingly, the 5-year breast cancer-specific survival rate was highest in patients having DIEP flap surgery after 2008 – 92.4 percent in the DIEP flap group versus 87.4 percent in the control group.
The study design does raise some questions about selection bias. For example, all DIEP flap procedures in this study were performed at least 24 months after mastectomy. No DIEP flaps were performed at the same time as the mastectomy (‘immediate’ reconstruction). In addition, a larger number of patients in the DIEP flap group than the control group received adjuvant therapy.
While the survival rates between groups may have been influenced by patient selection, this study shows that patients with breast cancer undergoing DIEP flap breast reconstruction do NOT have a higher rate of breast cancer recurrence than patients undergoing mastectomy alone.
Does Fat Grafting Increase the Risk of Breast Cancer Recurrence?
Autologous fat grafting, or “lipofilling”, is widely used in conjunction with breast cancer surgery:
1. it can correct partial breast defects after lumpectomy
2. it is used in conjunction with other breast reconstruction techniques to optimize breast contour and improve the final cosmetic results after both implant-based and autologous (flap) reconstruction
3. it is the primary breast reconstruction technique in male breast cancer patients
4. it can fill in contour defects and improve chest soft tissue padding after mastectomy in patients choosing to go flat
Fat grafting has also been shown to improve scar appearance, improve breast pain, and even reverse the soft tissue effects of radiotherapy (such as fibrosis).
The procedure involves liposuctioning from one part of the patient’s body, purifying it and then injected into the breast. It can be performed in conjunction with other breast procedures or as a stand-alone procedure. There are several fat grafting techniques that are used by plastic surgeons. There is no “set way” that has been shown to be the best in terms of long-term results. However, studies have shown that regardless of the technique used, the collection, handling, and transplantation of the fat cells must be optimized to obtain the best long-lasting results.
Despite the associated benefits, fat grafting in patients with a history of breast cancer has been somewhat restricted by 2 main concerns: the fear that it can interfere with breast cancer imaging, and that the regenerative cells could increase the risk of local breast cancer recurrence.
Some of the injected fat can turn hard after lipofilling. This is known as “fat necrosis”. Areas of fat necrosis cause calcifications (macrocalcifications) on mammograms. However, previous studies have shown that these macrocalcifications do not interfere with subsequent detection of breast cancer. The question regarding the risk of recurrence remains a topic of debate due to animal studies that have shown adipose-derived stem cells can stimulate cancer growth in nude mice. Although we don’t truly know whether the interaction between human fat tissue and cancer cells injected in immunodeficient mice can accurately reflect what happens in people, this uncertainty has led to obvious concerns about lipofilling patients with a history of breast cancer, particularly after a lumpectomy.
A recent study aimed to answer whether patients with breast cancer treated with autologous fat grafting are at an increased risk of cancer relapse compared with those who receive conventional breast reconstruction alone. No significant difference in the rate of local recurrence was seen after a 5-year follow-up. These findings confirm the results of previous studies; there is no clinical evidence to suggest that autologous fat grafting increases the risk of local breast cancer recurrence.
