Adjuvant treatment with the drug showed a statistically significant improvement in disease-free survival of 33 percent versus patients on placebo, according to trial data.
Read MoreTop biotech analyst calls out Yellen
Adjuvant treatment, or additional treatment, is given after the primary treatment.
Patients in the trial were treated with neratinib after adjuvant treatment with cancer drug trastuzumab in women with early-stage HER2-positive breast cancer.
Cancer cells with above-normal levels of the HER2 protein increases breast cancer risks.
Read MorePrescription roulette: Are discount drug sellers safe?
Meanwhile, someone seems to have bet big in the options market that Puma would be a winner in the days before the positive results.
Whether the trading on July 15 is suspicious or not, the report showing a Puma drug's success against breast cancer in a late stage study clearly surprised some Wall Street analysts. Stifel reportedly had predicted a "grim" outlook for neratinib, and Cowen said the report showed surprisingly positive data.
Read MoreNajarian: 'Fishy' options trade ahead of Puma news
Neratinib, licensed from Pfizer, is also being studied in patients with non-small cell lung cancer and other solid tumors that have a HER2 mutation.
"It could be a biotech fund taking that big shot. The timing's great though," said OptionsMonster co-founder Jon Najarian, who pointed out options activity and called it "fishy." The stock was trading at $216 at mid-morning Wednesday, up 159 points or 242 percent.
The U.S. Securities and Exchange Commission declined to provide comment to CNBC on the options activity.
Puma did not respond to CNBC's request for comment.