If Raloxifene Prevents Bone Loss AND Breast Cancer, Why Is It Forgotten?

When a brand name drug loses its patent, the company that developed it often stops advertising it. The pharmaceutical industry likes to promote the latest shiny new medicine. That’s where the money is! Older medications that are available generically rarely get much support. Such seems to be the case for a drug called raloxifene (Evista).

Evista was approved by the FDA in December 1997 for preventing osteoporosis. In October of 1999 it got FDA’s green light for treating osteoporosis. Then in 2007 the agency gave the Eli Lilly Company the right to market raloxifene to treat women at high risk for invasive breast cancer.

The Lilly Company’s Enthusiasm About Evista (Raloxifene):

The company that developed Evista announced the breast cancer approval this way (September 14, 2007):

“‘The FDA’s decision marks a major milestone. For the first time, postmenopausal women with osteoporosis will have one treatment option that can help address two leading health concerns — osteoporosis and invasive breast cancer,’ said Gwen Krivi, Ph.D., vice president of Lilly Research Laboratories. ‘Further, postmenopausal women at high risk for invasive breast cancer will have an alternative therapy for invasive breast cancer risk reduction.’”

“EVISTA, a selective estrogen receptor modulator or SERM (recently classified by the FDA as an estrogen agonist/antagonist), is already approved for the prevention and treatment of osteoporosis in postmenopausal women. In July, the Oncologic Drugs Advisory Committee (ODAC) to the FDA voted to recommend approval for the new uses. Today’s decision and the positive recommendation from ODAC were based on data submitted in November 2006 in a new drug application (NDA), evaluating clinical results from approximately 37,000 postmenopausal women that spanned nearly 10 years.”

You will shortly read how Eli Lilly and Company got into deep trouble with the Justice Department about breast cancer claims. But first, some background on this fascinating compound.

Why Did Raloxifene (Evista) Disappear Almost Without a Trace?

Many women worry about breast cancer, especially if a relative is diagnosed with this challenging disease. Others fear weakened bones and fractures. These days many women get a bone mineral density (BMD) test (DXA or DEXA scan). It can reveal osteopenia (low bone density) or osteoporosis (weakened bones at increased risk for fractures). Once a test reveals a bone problem, doctors frequently prescribe women one of the many newer osteoporosis drugs.

One might imagine that a medication that does double duty in the fight against both breast cancer AND osteoporosis would have achieved a certain amount of staying power. That has not been the case for raloxifene.

At last count, raloxifene does not register in the top 300 prescribed drugs in the US. That means it seems to have been mostly forgotten by both physicians and patients. Instead, doctors prescribe a different SERM (selective estrogen receptor modulator) called tamoxifen to prevent breast cancer return after surgery.

Other options include aromatase inhibitors such as anastrozole (Arimidex), letrozole (Femara) or exemestane (Aromasin). Such medications are often prescribed after breast cancer surgery to prevent a recurrence. By the way, aromatase inhibitors may increase the chance a woman will develop osteoporosis and bone fractures.

How Does Raloxifene Work to Prevent Breast Cancer AND Osteoporosis?

To understand the double-duty benefits of raloxifene you have to understand what a SERM is. The idea that a drug could act as both an agonist and an antagonist is, in my opinion, a bit challenging for health professionals to grasp. That’s where the term selective estrogen receptor modulator (SERM) comes from.

One the one hand, raloxifene binds to estrogen receptors in bone. That means it is an “agonist” in bone. By activating estrogen receptors in bone it increases bone mineral density, enhances bone strength and reduces the risk for vertebral fractures (Cureus, Nov. 19, 2023).

Raloxifene has the opposite effect on breast tissue, however. There it acts as an estrogen “antagonist.” In other words, raloxifene blocks the effect of estrogen in the breast. Estrogen is a bit like fertilizer, especially for hormone-sensitive breast cancers. By blocking, or antagonizing, estrogen in the breast, the drug reduces the risk of invasive breast cancer.

Uterine Cancer Comparison:

One more tidbit about raloxifene vs. tamoxifen:

According to the American Cancer Society:

“Because tamoxifen acts like estrogen in the uterus, it can increase your risk of cancers of the uterus, including endometrial cancer and uterine sarcoma. It’s also linked to a higher risk of endometrial pre-cancers. The increased risk seems to affect women over 50, but not younger women.

“Raloxifene does not act like estrogen in the uterus and is not linked to an increased risk of uterine cancer.”

A Reader Shares Her Story with Raloxifene:

Q. My doctor prescribed raloxifene when I was in my 50s because my mother had died of breast cancer. She believed this drug would block estrogen from harming the breasts.

It must have worked, as I took it for 15 years without side effects and no bone problems. I stopped taking it then, on the grounds that there couldn’t be much estrogen left in my system. Eighteen months later I had a lumpectomy for an early tumor that was estrogen receptor positive. Get those mammograms!

A. When raloxifene (Evista) was first introduced more than a quarter century ago, it was for preventing osteoporosis. It works differently from other common osteoporosis drugs, bisphosphonates like alendronate (Fosamax) or ibandronate (Boniva). That’s because it acts through estrogen receptors.

Oddly, raloxifene behaves in distinct ways depending on the tissues. The bones respond as if they are getting more estrogen–so they get stronger–while it blocks estrogen’s effects in the breast.

A study of 7700 postmenopausal women found that those taking raloxifene were much less likely to develop estrogen receptor positive breast cancer (JAMA, June 16, 1999). In 2007, the FDA approved it for breast cancer prevention in high-risk women like you. It blocks the activity of estrogen in the breast and is considered effective for reducing the risk of breast cancer in postmenopausal women with osteoporosis (Oncology Reviews, April 10, 2025).

Side effects include swollen legs or fingers, hot flashes, leg cramps and, most worrisome, blood clots. That’s why doctors are supposed to weigh benefits against risks before prescribing it.

The American Cancer Society puts the blood clot risk into perspective:

“Both tamoxifen and raloxifene increase your risk of developing blood clots in a vein in your leg (deep venous thrombosis) or in your lungs (pulmonary embolism). These clots can sometimes cause serious problems, and even death. In the major studies looking at these drugs for breast cancer prevention, the overall risk of these blood clots over 5 years of treatment was less than 1%. This risk could be higher if you had a serious blood clot in the past, so these drugs are generally not recommended to lower breast cancer risk for anyone with a history of blood clots.”

Lilly and the Law:

Before the FDA approved Evista for reducing the risk of breast cancer, the Eli Lilly and Company got severely spanked by the Department of Justice. Remember, the FDA did not give the company permission to market the drug against breast cancer until 2007.

According to Forbes, November 1, 1999:

“Evista won approval for use against osteoporosis in December 1997, and Lilly put out a press release hyping the cancer-prevention angle–and drew fire from the FDA. Lilly then launched a $40 million ad blitz in 1998. The print and TV ads were supposed to tout only the osteoporosis claim, but the FDA later issued warning letters to Lilly for implying that Evista had won approval for preventing breast cancer.

“In the spring of 1998 a swarm of press reports noted that new data showed Evista prevented breast cancer without tamoxifen’s downside, an increased risk of uterine cancer. Lilly helped fuel the coverage by releasing its results at a major cancer conference.”

The Department of Justice released this statement on December 21, 2005:

“American pharmaceutical manufacturer Eli Lilly and Company agreed to plead guilty and to pay $36 million in connection with its illegal promotion of its pharmaceutical drug Evista, the Justice Department announced today. In pleading guilty to a criminal count of violating the Food, Drug, and Cosmetic Act by misbranding its drug Evista, the Indianapolis-based company agreed to pay a $6 million criminal fine and forfeit to the United States an additional sum of $6 million. In addition to the criminal plea, Lilly has agreed to settle civil Food, Drug, and Cosmetic Act liabilities by entering into a consent decree of permanent injunction and paying the United States $24 million in equitable disgorgement.

“Evista is approved by the FDA for the prevention and treatment of osteoporosis in post-menopausal women. As alleged in the information, under the provisions of the Food, Drug, and Cosmetic Act, a company must specify in its new drug application to the FDA labeling for all proposed intended uses for the drug. Once approved by the FDA, the drug may not be legally marketed or promoted for so-called ‘off-label’ uses – any use not specified in an application and approved by the FDA.

“The information alleges that the first year’s sales of Evista in the U.S. were disappointing compared to Lilly’s original forecast. According to the information, in October of 1998, the company reduced the forecast of Evista’s first year’s sales in the U.S. from $401 million to $120 million. An internal Lilly business plan noted that ‘Disappointing year versus original forecast.’ The information alleges that in order to expand sales of the drug, Lilly sought to broaden the market for Evista by promoting it for unapproved uses.

“The information alleges that Lilly’s strategic marketing plans and promotion touted Evista as effective in preventing and reducing the risk of diseases for which the drug’s labeling lacked adequate directions for use. According to the information, Lilly’s Evista brand team and sales representatives promoted Evista for the prevention and reduction in risk of breast cancer, and the reduction in the risk of cardiovascular disease. Under the provisions of the Food, Drug, and Cosmetic Act, Evista was misbranded when its labeling did not bear adequate directions for each of these intended uses. As alleged in the information, Lilly promoted Evista as effective for reducing the risk of breast cancer, even after Lilly’s proposed labeling for this use was specifically rejected by the FDA.”

The FDA Did Eventually Approve Evista (Raloxifene) for Breast Cancer Prevention:

Here are the FDA’s permitted indications for Evista:

“• Treatment and Prevention of Osteoporosis in Postmenopausal Women

“• Reduction in the Risk of Invasive Breast Cancer in Postmenopausal Women with Osteoporosis

“• Reduction in the Risk of Invasive Breast Cancer in Postmenopausal Women at High Risk of Invasive Breast Cancer”

You can read more about side effects, interactions and special precautions at this link.

Final Words About Raloxifene:

We are neither advocates nor critics of this medication. We are somewhat surprised that most physicians have seemingly stopped prescribing raloxifene for osteoporosis and breast cancer prevention. Newer medications are far pricier. The price with a GoodRx coupon is, at the time of this writing, about $69 for 90 tablets. That is a 3-month supply.

There are now many other medications for reducing the risk of osteoporosis. But they too have side effects. You can read about Prolia at this link and Reclast at this link.

Please share your own experience with tamoxifen or raloxifene in the comment section below. If you have taken a different medication to prevent osteoporosis or recurrent breast cancer, please tell us how that went.

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