Shortly after the discovery of x-rays by Wilhelm Roentgen in 1895 and of radium by Marie Curie in 1898, it was realized that ionizing radiation could be used against breast cancer. In 1905, the first radiologic textbooks proposed the use of radiation therapy for unresectable primary tumors, including breast cancer. In 1937, Sir Geoffrey Keynes, a surgeon in England, pro­posed the notionof radiumneedle insertion into operable breast cancer as an alternative to mas­tectomy. He reported 5-year local recurrence rates and survivals similar to what was being obtained with radical mastectomy. Similar resultswere obtained fromthe Curie Foundation in Paris and other European investigators.

Ionizing radiation can take either an electro­magnetic form, as high-energy photons, or particulate forms, such as electrons, protons, neutrons, alpha particles, or other particles. Most radiation is delivered through either elec­trons or photons. Electrons interact directly with tissue causing ionization, in contrast to photons, which affect tissues by the electrons that they eject. Electron beams deliver a high-skin dose and exhibit a rapid fall-off after only a few centimeters, so they are typically only used to treat superficial targets such as skin cancers or lymph nodes within a few cen­timeters of the surface of the body. Irradiation with photons can penetrate deeper into tis­sues. Photons can cause the ejection of elec­trons by a variety of methods (Fig. 15–1), but the most important is the Compton Effect,in which a photon collides with an electron, transferring some of its energy to the electron and scattering both the photon and the elec­tron in various directions. The photon can then undergo additional interactions (with a subsequently lower energy), while the electron begins to ionize with the energy it gained from the photon.

subsequently interact with target molecules. During their brief life span, electrons and free radicals interact with molecules in a random fashion. If they interact with molecules that are not crucial to cell survival, the effect of the radiation will be harmless. If they react with biologically important molecules, the effect will be detrimental. Molecular oxygen prolongs the life of reactive radicals, increasing the likelihood that it will have a detrimental effect. This is why tumor hypoxia tends to increase resistance to radiation. Antioxidants reduce the life span of free radicals by combin­ing with them, thereby also increasing cellular resistance to radiation.

interval. As the time interval between the frac­tions increases, the surviving fraction of the cells also increases because the cells are able to repair double-strand DNA breaks. Further­more, if the time interval is sufficiently long, the cells will once again begin to proliferate in a process known as repopulation.

operable breast cancersbegan and laid the foun­dation for breast-conserving therapy (BCT). Today radiation therapy has multiple uses in the management of breast cancer, such as the treatment of chest wall recurrences or palliation of bone metastases, but the primary use of radi­ation is in the management of early therapy as either a component of BCT, or chest wall irradi­ation following mastectomy. The optimal local management of breast cancer requires coordi­nation between the surgeon, the plastic sur­geon, and the radiation oncologist.

demonstrated a 5-year local recurrence rate of 7% for breast conservation with radiation ther­apy and 26% when radiation therapy was excluded. The most recent update of the ECGTCG meta-analysis demonstrates that the 15-year breast cancer mortality risks were also significantly lower in the patients who received radiation therapy (30.5 versus 35.9, p ¼ 0.002).

A pooled analysis of mortality data from 13 randomized trials also showed a worse survival in women who did not receive radiation ther­apy, with an 8.6% excess mortality. This data clearly demonstrates that improved local con­trol does impact survival, and women with an exceedingly high risk of in-breast recurrence with BCT compared to mastectomy may be better served by the latter. It also establishes that radiation is a critical component of breast conservation therapy.

One subset of patients for whom the avoid­ance of radiation seems possible is older women with hormone receptor positive tumors. Several retrospective series of conservative surgery alone in older women have shown varying rates of local recurrence, but similar distant recur­rence and survival rates. Two randomized trials have shown comparable results. In a Canadian trial randomizing women over the age of 50 undergoing lumpectomy with adjuvant tamox­ifen to radiation or none, radiation therapy sig­nificantly decreased the risk of local recurrence (17.6% versus 3.5% at 8 years), but did not appear to impact rates of distant metastases, overall survival, and the number of deaths as a result of breast cancer. However, given what we now appreciate about local control and over­all survival, this local recurrence rate seems uncomfortably high. A Cancer and Leukemia Group B (CALGB) trial of women over the age of 70 also showed a difference in the risk of local recurrence in women treated with tamoxifen with or without radiation therapy (4% versus 1%), but no impact on overall survival (86% versus 87% at 5 years). Rates of mastectomy for local failure were also similar. Although the Canadian trial included tumors up to 5 cm, the CALGB trial was limited to tumors less than 2 cm. Thus, in selected women over the age of

70 with small ER-positive breast cancer, treat­ment with lumpectomy and tamoxifen alone may be a reasonable option.

It is often presented to patients that one of the advantages of mastectomyover BCT is that radi­ation therapy will not be necessary. However, chest wall recurrence after mastectomy alone is not an infrequent event. The risk of local­regional failure after mastectomy increases with both increasing tumor sizeand increasing num­bers of involved axillary nodes. Trials of post­mastectomy radiation, accruing patients in the 60s and 70s, demonstrated that postmastec­tomy radiation could decrease chest wall recur­rences. Similar to the experience with BCT, however, these trials did not demonstrate any significant effect on overall survival. In fact, there was even the suggestion of a decreased survival. But as before, these trials were under­powered to detect a small survival benefit, and they mostly involved radiation techniques that had increased morbidity and mortality compared to today’s approaches.

Figure 15–4. Linear accelerator.

ciated with increased rates of relapse. struction. If the patient is node positive, reconstruction can be delayed, especially if tis­sue expanders were planned.

the undesirable effects resulting from lower-

energy radiation (such as orthovoltage, 150 to

500 kV, or supervoltage, 500 to 1000 kV). The

tage radiation therapy are linear accelerators When adjuvant chemotherapy is necessary, radiation will follow the chemotherapy. If neg­ative margins were not achieved and the initi­ation of chemotherapy is being delayed by the need for reexcision, it is reasonable to proceed

tion. Most simulation today is accomplished Either way, negative margins must be obtained before beginning radiation. Concomitant che­moradiotherapy may minimize the time nec-

When chemotherapy is not used, radiation should follow surgery once adequate time for healing has been allowed (typically 4 weeks). Sometimes this may be delayed because of the formation of a seroma. Repeated aspirations of the seroma during therapy will cause fluctua­tions in the breast contour and the skin marks. Thus, the need to aspirate the seroma must be balanced against when radiation will com­mence or conclude and the patient’ssymptoms. Radiation may also be delayed by the patient’s inability to abduct and maintain the arm in

using computed tomography (CT) scanning (Figure 15–5). With modern CT technology, virtual simulation allows for better visualiza­tion of the breast, chest wall, and most impor­tantly the relation to the lung and h eart, th us minimizing damage to normal tissues. Minimizing toxicity to the underlying heart and lung must be carefully considered in the treatment plan. The patient is scanned with the breast in an immobilization device so that the patient position is reproducible from day to day. Typically this is in the supine position, but the prone position can be used for the patient with a pendulous breast, provided ade­quate coverage of the tumor is achieved. The scanned information is then brought up on the treatment planning console and the treatment plan is created. The target volume for whole breast radiation therapy extends medially to the middle of the sternum, and lat­erally to the midaxillary line. The inferior edge of the field is approximately 1 cm below the inframammary fold in the intact breast or the contralateral inframammary fold when treating the chest wall. Superiorly, the field typ­ically ends atthe base of the head of the clavicle.

computer-based quality assurance. The key to optimal radiation therapy is the meticulous technique reviews by the radiation oncolo­gists, physicists, dosimetrists, technologists, and remainder of the treatment team.

Fatigue—Fatigueis one ofthe most common