Agents of Change

Photo of Dr. Pullatt during the robotic DIEP flap harvest
Dr. Rana C. Pullatt (right) during the robotic DIEP flap harvest.

Specialists at the MUSC Breast Center innovate to advance care for women with breast cancer

by Kimberly McGhee and Tonisha Kearney-Ramos

The Breast Center at MUSC Hollings Cancer Center, led by renowned breast surgeon and translational cancer researcher Nancy K. DeMore, M.D., offers women with breast cancer multidisciplinary and comprehensive care delivered by specialists who have devoted their careers to combating the disease. Care teams comprise breast cancer surgeons, medical oncologists, radiation oncologists, genetic counselors, pathologists, and nurse navigators who have completed fellowships or received other specialized training in the management of breast cancer. The team meets weekly at a breast cancer tumor board to discuss cases, so that patients can be assured that all of their care providers are operating from the same game plan and that all treatment decisions draw upon the collective wisdom of the team. That spirit of collaboration and the desire by team members to continually optimize the screening, diagnosis, and surgical management of breast cancer fosters an environment where innovative solutions to address limitations in current standard-of-care techniques are encouraged. Providers act as agents of change, working to continually improve patient experience and outcomes.

Screening and Diagnosis

Limitation: Although traditional 2-D digital mammography has saved many lives, it does not always accurately identify abnormalities in dense breast tissue.

Innovation: Digital breast tomography

Digital breast tomography (DBT), also known as breast tomosynthesis or 3-D mammography, is a procedure in which several low-dose x-rays are taken at different angles; these source images are then reconstructed into multiple thin slices that can be scrolled through one by one. This helps to reduce diagnostic uncertainties caused by the overlap of normal fibroglandular breast tissue. It is performed in addition to traditional 2D-mammography, takes only a few seconds longer but requires additional radiation (still within FDA-prescribed limits). Studies have shown that DBT can increase breast cancer detection and lessen the likelihood that patients will need to return for additional imaging. Although DBT is now available at Hollings and MUSC East, as well as many other sites in the country, randomized clinical trial (RCT) data are needed to assess its diagnostic value.

Radiologists Susan J. Ackerman, M.D., and Dag Pavic, M.D., will be the principal investigators for the Hollings and MUSC East sites, respectively, of TMIST, an RCT that will begin recruiting in mid-2017 and aims to enroll 165,000 asymptomatic U.S. and Canadian women between 45 and 74. Participants will be randomized to either 2D mammography or DBT and followed up for four years so that the incidence of advanced cancer can be compared in the two groups. Results from this trial should provide a definitive answer as to whether DBT should be more widely adopted in the clinic.

Limitation: Breast biopsies have a high rate of false positives, i.e., a number of tissues thought to be abnormal on imaging turn out to be normal when biopsied.

Innovation: SFRP2-targeted molecular ultrasound

DeMore is collaborating with bioengineering colleagues at The University of North Carolina – Chapel Hill (UNC) to optimize SFRP2-targeted molecular ultrasound. DeMore’s laboratory identified a novel stimulator of tumor angiogenesis (secreted frizzle-related protein 2 [SFRP2]), showed that it was overexpressed in breast cancer and created an antibody to target it. Her UNC colleagues have conjugated that antibody to a microbubble containing contrast agent. By targeting SFRP2, the antibody selectively steers the microbubble to cancerous cells, which then bind with the contrast agent. Areas of high contrast suggest cancerous tissue in need of biopsy. In an article published online on March 23, 2017 by PLOS One (doi: 10.1371/journal.pone. 0174281), DeMore and her UNC collaborators demonstrated the feasibility of this approach in a preclinical tumor model. DeMore has a large grant from the National Institutes of Health to test the new approach in preclinical models of various types of breast cancer. Although still years out of the clinic, the technique could one day help prevent unnecessary biopsies.

“The hypothesis is that if you had a lesion that did not enhance with contrast agent, that would be predictive of it not being a malignancy, and then you wouldn’t need to have a biopsy,” explains DeMore.

Surgical Management

Limitation: Wire localization of nonpalpable breast lesions, which is typically performed on the same day as surgery, causes logistical challenges that reduce operating room efficiency.

Innovation: Savi Scout®, a new FDA-approved localization technique

Because most biopsies today are of nonpalpable lesions identified by mammography, localizing the lesion to be surgically excised typically involves the insertion of a wire into the abnormal tissue by a radiologist under mammographic guidance. Wire localization requires the patient to undergo a second invasive procedure and, because it is typically performed the day of surgery, can lead to logistical difficulties for the operating room (OR).

The MUSC Health breast surgical oncology team, which includes DeMore, Andrea M. Abbott, M.D., David J. Cole, M.D., and Mark A. Lockett, M.D., is now offering Savi Scout®, a novel localization technique in which the radiologist places a reflective chip next to the titanium clip that was inserted at the time of biopsy (to guide the surgeon in case a malignancy was found). The reflector chip can be implanted from one to 30 days before surgery. On the day of surgery, the surgeon uses a probe that bounces radiofrequency off the reflective chip to localize the clip and the tissue requiring excision. Because this technique uncouples the localization and surgical excision procedure, enabling them to be performed days apart, OR efficiency is improved, and delays in surgery are less likely.

Innovation: Direct localization of the titanium clip with a metal detector (investigational)

Like SaviScout, other novel localization techniques, including magnetic seed localization and radioactive seed localization, promise improved OR efficiency because the tiny magnetic or radioactive seed can be implanted well in advance of surgery, avoiding last-minute logistical delays. The surgeon then uses the appropriate probe to locate the seed and the abnormal tissue for excision. However, all three localization procedures share the same disadvantage: patients are required to undergo a second invasive procedure and must take a second day off work. In addition, radioactive seed localization could pose a radiation hazard should the seed break.

DeMore wondered whether a metal detector could be developed to detect the titanium clip directly, avoiding the need for an invasive localization procedure before surgery. Titanium is the metal of choice for the marker clip, which will remain in the patient indefinitely if the tissue is noncancerous and no surgery is required, because it is very weakly electromagnetic and will not be detectable on airport scanners or interfere with MRI.

DeMore consulted with Clemson bioelectrical engineer Delphine Dean, Ph.D., to see if developing such a detector was possible. Dean challenged her design class to draw up plans for the detector, which they did, and, within a matter of months of having the idea, DeMore had a prototype she could test in specimens of breast tissue. The next step is to produce a prototype that is compliant with Good Manufacturing Practice that can be taken forward into clinical trial.

In 2017, the titanium detector won the new technologies award at the Innovations in the Operating Room conference hosted by the Society of Surgical Oncology. DeMore also won a local “shark tank” contest — the Southeastern Medical Device Charleston Road Pitch Competition — and competed in the regional contest in Atlanta.

Limitation: In traditional mastectomy, the nipple is removed along with the rest of the breast, requiring nipple reconstruction or tattooing as the last phase of breast reconstruction.

Innovation: Nipple-sparing mastectomy followed by prepectoral implant

The loss of a breast can mar a woman’s self-image and shake her sexual confidence. Nipple-sparing mastectomy, in which breast glandular tissue is extracted through a small incision while the skin and nipple of the breast remain intact, minimizes scarring and sets the stage for a more natural, cosmetically pleasing breast reconstruction.

The MUSC Health breast surgical oncology team collaborates with plastic surgeons Jason P. Ulm, M.D., and Kevin O. Delaney, M.D., who offer a novel reconstruction technique called prepectoral implant that can be performed either immediately after nipple-sparing mastectomy or some time thereafter. Unlike traditional implants, which are placed under the chest muscle and require cutting of the pectoralis major, prepectoral implants are placed above the muscle just under the skin, considerably reducing patient pain and morbidity. The appearance of “rippling” under the skin that was an early drawback of the technique has been overcome by the availability of lipofilling, in which fatty tissue harvested from the abdomen is layered over the prepectoral implant, improving its appearance. The reconstructed breast looks very natural, boosting patients’ self-image and sexual confidence. Patients should be aware, however, that the implants do not feel like natural breasts.

To view voiced-over surgical photographs from a nipple-sparing mastectomy by Dr. Abbott followed by a prepectoral implant by Dr. Ulm, visit MUSC Health Medical Video Center and select oncology from the dropdown menu of specialties.

Limitation: The long incision required for traditional deep inferior epigastric perforator (DIEP) flap harvest for breast reconstruction causes considerable pain, extends recovery, is vulnerable to hernia and can weaken abdominal muscles.

Innovation: Robotic DIEP flap harvest

For more than 20 years, DIEP flaps have been used to provide living tissue for breast reconstruction. A flap of tissue and fat, along with the associated vasculature, is harvested from a patient’s abdomen or flank and used to reconstruct a breast. The vessels attached to the excised flap are connected to the internal mammary artery and vein to ensure a blood supply for the new breast. Traditionally, DIEP flap harvest has required an incision along the entire abdominal wall to provide the surgeon with access to and visualization of the deep inferior epigastric artery and veins so that the blood vessels could be safely dissected from surrounding tissue. This necessitates the cutting of the abdominal fascia from just underneath the belly button to the groin crease.

Wondering if a robotic approach would enable a smaller incision and less morbidity, Delaney contacted Rana C. Pullatt, M.D., a highly skilled and experienced robotic surgeon who directs the robotics program for the Department of Surgery at MUSC Health, to discuss the possibility. The two agreed the approach had merit and, in February 2017, they together performed the first-ever robot-assisted DIEP flap harvest.

Instead of the 15-cm incision that would have been required for traditional DIEP flap, Delaney was able to make only a 2.5 to 3.0-cm incision to free the tissue and fat and dissect the portion of the vessels that was accessible from outside the abdominal wall. Pullatt then made a few very small portholes where he was able to insert an endoscopic camera and dock the robot. Then, seated at a console, and with access to endoscopic images, he guided the hands of the robot to dissect the vessels underneath the abdominal fascia from the surrounding tissue until he reached the point where Delaney had stopped. Delaney was then able to lift the flap out with the vessels attached. Although the procedure took a little longer than the traditional surgery, it was much less invasive and resulted in less pain and morbidity for the patient.

More research is needed to identify the patients most likely to benefit from the new approach, but Delaney and Pullatt suspect it will be best-suited to those in which traditional DIEP flap harvest is difficult, such as obese patients or those with a great deal of intramuscular mass.

To watch footage of the robotic DIEP flap harvest narrated by Dr. Pullatt, visit the MUSC Health Medical Video Center and choose oncology from the dropdown menu of specialties.