Treatment
Prospects have improved with the development of new drugs that interfere with unique biochemical pathways driven by cancer-causing mutations. The translation of molecular findings into practical treatments is exemplified by the recent approval and acceptance of Herceptin® in clinical practice.This antibody targets the cell surface marker for a particularly lethal subtype of breast cancer, and is active only in patients carrying that marker. Identifying patients likely to benefit was a major challenge, solved by rigorous testing of large populations in early clinical trials. Recent randomized studies prove that carefully selected patients enjoy markedly improved outcomes if Herceptin is combined with standard chemotherapy at the time of original diagnosis. Other new US Food and Drug Administration (FDA)- approved biologic agents, (Avastin®, Tarceva®, and Erbitux®) cannot be prescribed with confidence (or insurance coverage) until the logistical hurdles of patient selection and definition of optimal combinations are solved. Similarly, investigational agents such as sorafenib and lapatinib are poised for approval but will not be used widely until the same barriers are breached.

Another area of hot research is the genotyping of cancer cells to determine whether a patient will or will not benefit from specific treatments, including standard hormone or chemotherapy, or new biologics. In particular, the OncotypeDX® assay of 21 cancer-related genes predicts patient outcome, and can guide the drug therapy of post-menopausal women at the time of initial diagnosis. In a perfect future, effective therapies will cure rather than palliate, and they will be used only on those patients who will benefit from them. This is known as the testicular cancer paradigm treatment can cure, even if used in advanced disease. Currently, medical treatments extend the lives of breast cancer patients by approximately five years beyond that expected with only surgery or radiation. New treatments will buy even more survival time, but no cures are on the horizon. Side effects of current cancer therapies range from none to debilitating, and individual patient costs can exceed US$100,000 per year.

Screening
Screening is widely accepted, despite remaining doubts about overall benefit and cost-effectiveness. Strong opinions promote its use, based on the assumption that cancers discovered early can be excised and cured. Randomized trials encompassing half a million women have the statistical power to demonstrate a relative benefit for screened versus unscreened women. However, in absolute terms, only six per 10,000 women benefit from regular screening, whereas several thousand will undergo additional tests and biopsies. A recent comparison of women diagnosed with either early or advanced breast cancers found that similar proportions had participated in screening.

The notion that timely surgery can cure is becoming outdated as it ignores two important bodies of knowledge. Firstly, most screen-detected breast cancers are slow-growing, with a low likelihood for harm. Finding and excising these low-risk cancers, many of which are destined to remain dormant, makes only a small impact in overall cancer mortality, while committing a large number of women to treatment. In addition, pre-cancerous tissue, which is often found via screening, is frequently over-treated, as a clear consensus on optimal management is lacking. Ironically, screened populations have approximately 50% more breast cancers than unscreened populations, because screening detects so many low-risk cases that would never become clinically significant. Consequently, many healthy women are labeled cancer patients. Meanwhile, the most lethal cancers are often missed by screening mammograms either because they cannot be differentiated from surrounding normal tissue, or because they grow quickly in the interval between screening examinations. Despite the promise of digital mammography, it has not been proven to be better than standard technology. A screening test that preferentially finds lethal cancers is needed.