Editorial by: James A. Edney, MD, Professor of Surgery and Chief of Surgical Oncology, University of Nebraska Medical Center, Omaha, Nebraska.

The modern management of breast cancer is evolving at a rapid rate. This editorial outlines the treatment advances that the author anticipates within the next decade.

 Within the next several years the Nipple will become the new target for early detection. The nipple is uniquely positioned to provide this information. The intraductal approach via nipple fluid aspiration and ductal lavage of the tributaries, where most breast cancer originates, will become the “Pap Smear” for the breast allowing us to recognize early morphologic changes years before small cancers would be detectable by mammography. By accessing the nipple we will be able to identify breast cancer or its precursors up to four years before it would be detectable by mammography.

Those individuals with a suspicious or frankly positive ductal lavage will undergo “ductoscopy”. This technology has already been developed. A disposable micro-endoscope as small as 0.9 mm. in diameter with working channels allowing the introduction of diagnostic and therapeutic tools is already available. In addition to potentially identifying intraductal abnormalities years before they are visible by mammography, this technology will allow future surgeons to use this as an aid in planning the extent of surgical resection minimizing the amount of tissue requiring removal.

Work is underway to identify biomarkers for susceptibility to breast cancer or recognize those individuals who may be harboring an occult cancer too small to be identified even with the most sophisticated imaging technology available. In our own laboratory we are analyzing breast tissue specimens harvested from patients with and without breast cancer and have found estrogen metabolites and conjugates [e.g. 4-catechol estrogen] up to four times higher in breast cancer patients than in the non breast cancer controls. These results are the initial ones in studies designed to identify serum markers to identify those individuals with occult disease and those who are at greatest risk. Through Genetic Engineering strategies will be developed to prevent breast cancer altogether in selected subsets of patients.

Within the next 10 years lumpectomy for small tumors will be replaced by tissue ablation. The technology is currently available and feasibility trials are underway. Radio- Frequency ablation, technology that is widely available and commonly used in the management of neoplasms of the liver, is being evaluated as primary management of selected breast cancers. In this technique, the probe is percutaneously placed, usually by ultrasound guidance into the tumor. Thermal energy is produced as the ions in the breast tissue surrounding the prongs attempt to follow the alternating current, thus creating frictional heating. As a result the breast tissue itself, not the probe, creates the heat to destroy tumor cells.

Investigators are examining the role of tissue freezing as an alternative to surgical excision. Like Radio-Frequency ablation, cryoablation requires ultrasound visualization of the lesion for performance of the procedure.  Just as in the management of liver metastases, the objective is to visualize an “ice ball” around the lesion to assure adequate margins while preserving surrounding normal tissue.

Work is currently underway evaluating laser ablation of tumors using the same stereotactic guidance technology currently being used for minimally invasive breast biopsy. The Laser needle is inserted into the center of the tumor, the stylette is removed and the laser emitting optic fiber is inserted through the needle. A second probe is inserted parallel and 1 cm adjacent to the laser needle to monitor tissue temperature and a predetermined amount of laser energy is delivered to the tumor.

These methods of “ablative” therapy will be ideally suited for the treatment of the smaller tumors, less than 2 cms. in diameter, that are being detected with increasing frequency in screening programs and will replace surgical excision. As a cautionary aside, the surgeon with limited imaging skills will no longer be the primary provider for women with breast disease.

For many patients pondering their treatment options, the protracted five to six week course of radiation therapy, essential for breast conservation, weighs heavily in their decision to undergo mastectomy. Studying the pattern of clinical recurrence, over 80% of local recurrences after breast conservation surgery occur at the site of the original resection. Preliminary work indicates that localized radiation to the site of resection alone may produce equivalent results to whole breast radiation. Using simplistic technology already available, at the time of initial operation the surgeon may leave behind a catheter with a balloon attached to the end within the cavity of resection. The balloon is then loaded through the catheter with a radioactive agent for five to ten minute treatments twice a day for five days.

If 5 days seems too long, intraoperative radiotherapy will replace postoperative treatment. Umberto Veronesi from Milan has done preliminary trials with breast conserving surgery plus intraoperative radiation. He has shown that it is possible to deliver up to 21 Gy intraoperatively, which biologically is identical to the 55 Gy of external beam treatments now being used.

Within several years it will be possible to offer all local and regional therapy including tumor ablation, axillary sentinel node biopsy, and intraoperative radiotherapy, providing all local regional treatment in a one hour operation as opposed to the 8-10 weeks now necessary.

As we gain a better understanding of the genetic aspects of breast cancer and the specific prognostic indicators for selected patients that promote local recurrence and facilitate the development of systemic metastases, we will develop “smart drugs”, such as Herceptin that will attack specific genetic abnormalities for appropriate patients, eliminating the need for the current “shotgun” approach used to treat large numbers of patients with cytotoxic agents. Basically Herceptin is a “smart drug” which blocks the Her-2/neu receptors on the surface of the cell of those individuals who have been identified as “overexpressing” the Her-2/neu gene and prevents growth factor molecules from attaching.

Within the next 30 years our current approach to breast cancer will be obsolete. Public health screening of 90% of the women with more sophisticated breast imaging, including digital mammography and Magnetic Resonance Imaging will further reduce the mortality to the 10% range. “Pap Smears” of the breast using ductal lavage in concert with ductal endoscopy will identify breast cancers at such an early stage that we will be able to treat over 90% of patients with “minimallistic” procedures using radiofrequency probes, laser ablation, or cryotherapy probes under stereotactic guidance. In these early tumors axillary metastases will be uncommon and will be detected by sentinel node biopsy. Axillary node dissection will be rarely indicated.

Mastectomy will be reserved for the rare patient with multi focal cancer or therapeutically resistant or recurrent cancer. Patients will receive localized radiation therapy delivered intraoperatively only to the excision site to sterilize the surgical margins. Many patients will be able to avoid radiation therapy altogether because of the extremely small size of the tumor.

Medical oncologists will treat many fewer breast cancer patients and of those, most will receive “smart drugs” based on genetic indicators as opposed to cytotoxic chemotherapy. New drugs will be custom designed to treat specific genetically identified abnormalities. Anti-angiogenic compounds or gene manipulation of selected patients will offer possible hope for the small number of patients with metastatic disease.

Within the next 15-20 years current treatment will be unrecognizable. Just as we now recall the “Halsted Era” when insufficiently radical breast surgery was considered nothing less than surgical cowardice, within the next several decades we will look back at the treatment modalities we are using today as drachonian and unnecessarily mutilating.

Gov. Dave Heineman Friday announced the official opening of the new 565 square foot Nebraska Center in Tokyo, Japan.

Led by Executive Director Koji Nagasaka, six Nebraska Center staffers will promote the state’s products and services, participate in Japanese trade shows, introduce Nebraska and Japanese business owners and operators, conduct market research, undertake marketing campaigns and other focused activities that help the state compete there.
 

“Nebraska has had a strong relationship with Japan,” Gov. Heineman said. “With the opening of this office, we hope to pursue an even stronger partnership over the long-term by enabling Nebraskans to work more closely with Japanese companies on business investment and development efforts. The Japanese place a high importance on personal relationships and interactions, and having a physical presence in the country is essential to expanding our opportunities for trade.”

Joining the Governor for the announcement were Nagasaka, Richard Baier, director of the Nebraska Department of Economic Development (DED), and Nizar Mamdani, executive director of the Office of International Healthcare Services at UNMC and The Nebraska Medical Center, two of the many organizations supporting the effort.
The center is located in the Shinjuku District, a business hub known for its high-rise landscape, including the Tokyo Metropolitan Government Towers. Located a short walking distance away is Japan’s busiest railway station, Shinjuku Station, which transports 2 million passengers daily.

“The international program at the medical center has grown to over 100 strategic global partners in 41 countries and each year facilitates bringing hundreds of international patients for treatment, as well as many international researchers, students and prominent speakers to Nebraska,” Mamdani said.

“Having a physical presence in Japan is truly a key for further expansion of the medical center’s Asian initiatives in the areas of patient care, research, biomedical, biotechnology, education and training. We know that the establishment of this office will drive our strategic international programs to the next level,” Mamdani said.

Nebraskans who are in Japan conducting business can use the office’s computer, telephone, fax and other services between meetings and travel.

Among the Trade Offices’ many services are researching, contacting and meeting with potential Japanese partners, providing basic translation and interpreting services, assisting with trade shows, marketing entry strategy recommendations, providing in-country assistance and selective visits with companies, assisting with hotel and travel needs, and coordinating meetings with Commercial Attache, JETRO, Shizuoka, and other Japanese partners.

“Mr. Nagasaka’s experience will be key to helping Nebraska achieve its full potential in Japan,” Gov. Heineman said. “The Japanese place a very high importance on personal interactions and spend a great deal of time building relationships and developing trust.”

Nagasaka was employed for most of his career at Itochu Corporation, the world’s 17th largest company, and one of Japan’s largest trading houses involved in the aerospace, textile, agricultural, biotech, chemical, logistics and bio fuels industries. For 17 years, he worked at Itochu offices in New York and Chicago, as manager of the Oilseeds section, and executive vice president of Cigra Inc., a subsidiary company of Itochu, in grain collection and export, respectively.

His main activity was exporting U.S. agriculture products to Japan. He also traded with Brazil, China, Denmark, Norway and Germany. While living in Japan, he managed Itochu’s Soybean Section. During his time in New York, he was transferred to Cargill Incorporated and stationed in several different cities, including Central City, Neb., to learn more about grain distribution in the U.S.

Nagasaka also served as president of Kamigumi Air Cargo Service Inc., an Itochu logistics subsidiary, and as executive vice president and owner representative of Kato Real Estate Corp., another Itochu subsidiary. Most recently, he served as deputy secretary general for Itochu Shayu-Kai, a nonprofit organization serving retired employees of Itochu Corporation.

In addition to DED and UNMC, other center partners include Election Systems and Software, Omaha; Lincoln Chamber of Commerce; Nebraska Diplomats, Lincoln; Greater Omaha Chamber of Commerce; First National Bank, Omaha; Oxbow Pet Products, Murdoch; Bruckman Rubber, Hastings; Werner Enterprises, Omaha; Nebraska Corn Board, Lincoln; Kawasaki, Lincoln; Nebraska Public Power District, Columbus; and Omaha Public Power District, Omaha.