Fisher was initially reluctant to relinquish his research on liver regeneration and transplantation and to take up the study of breast cancer and other malignant diseases, but he became intrigued by the subject of tumor metastasis.

[14] Fisher later said that after that NIH meeting, "I discovered how little information there was related to the biology of breast cancer and what a lack of interest there was in understanding the disease.

Giving up the liver regeneration and transplantation research in which he had been engaged, he began, along with his brother Edwin, a member of the University of Pittsburgh's pathology department, to study the biology of tumor metastasis.

[5][11] In 1958, Fisher took part in the first randomized clinical trial examining the results of systemic therapy following radical mastectomy for breast cancer.

At that time, moreover, "researchers theorized that women died of breast cancer despite radical surgery because tumor cells were dislodged during the operation.

This was "that breast cancer was a systemic disease in that tumor cells were likely to have been disseminated throughout the body by the time of diagnosis and that more expensive locoregional therapy was unlikely to improve survival".

Instead, a lumpectomy, in which only the tumor itself and a small amount of surrounding tissue are excised, would likely be just as effective and would have the added advantage of not causing disfigurement.

Fisher's work fundamentally changed the understanding of breast cancer and improved and extended the lives of thousands of women.

"[7] Fisher was "the first to show that less-invasive lumpectomy surgery treated breast cancer just as effectively as did disfiguring radical mastectomies."

Fisher discovered "that breast cancer metastasis is not solely determined by anatomic considerations, but is also influenced by biologic activity of both the tumor and the host".

[14] Aside from utterly transforming the treatment of breast cancer, Fisher's pioneering of "the multicenter randomized clinical trial set a standard for the scientific evaluation of therapy for many other diseases".

Upon being questioned by Fisher, the researcher, Dr. Roger Poisson at St. Luc Hospital, "admitted that he had falsified data for years to get unqualified patients into trials."

To ensure that Poisson's bad data had not "affected the outcome of the lumpectomy trial, Fisher reanalyzed the study" and found that the results were still valid.

"He notified the federal officials at his granting agency, the National Cancer Institute, of the problem with the errant researcher", and continued his work.

"[14] The national media reported in 1994 that Poisson had falsified data in 99 cases and that both Fisher and the NCI, under whose auspices the research was being done, had kept this information from the public.

One journalist's interpretation of the episode was that "the same self-assured and pugnacious attitude that had helped him triumph over surgical conservatism” had “landed him in hot water".

According to the article, "his reputation was in ruins....It was hard to believe that this humbled man had been, for decades, the bold field marshal of hundreds of staunchly independent surgeons, thousands of dedicated patients, millions of research dollars....It was hard to believe that the vast clinical network he had built up and run from a crowded headquarters at the University of Pittsburgh had slipped out of his control.

The article noted, to be sure, that some members of the scientific community "flatly refus[ed] to believe Bernard Fisher could commit bad science," quoting New York cancer researcher Dr. James Holland as asking.

Sharon Batt accused Fisher in her book, Patient No More: The Politics of Breast Cancer, of a "shocking breach of trust".

After being removed from his position at the NSABP, and being publicly accused by the University of Pittsburgh and NCI of having knowingly published false data, Fisher filed a defamation lawsuit.

[6] In autumn 1997, six weeks before his case was set to go to trial, Fisher accepted an apology from the university and a cash settlement from the defendants and agreed to withdraw his lawsuit.

After the settlement was announced, Fisher said that the lawsuit had not been about money, which, he indicated, “could hardly compensate for the 3½ years lost from his work,” but about “truth and justice.” He hoped that the settlement would “act as a deterrent to those who would disregard due process and the First Amendment right to freedom of speech.”[19] Responding to the charge “that he had not properly audited the data submitted by other researchers, had published papers knowing that some data had been falsified, and had been slow to publish corrections,” Fisher pointed out “that it was NSABP investigators who first uncovered the data falsification and it was the NSABP that told authorities about the problem.”[18] The apology from the university included stating "sincere regret at any harm or public embarrassment that Dr. Fisher sustained which was in any manner related to the activities of the University of Pittsburgh, and/or its employees," and "that at no time was Dr. Fisher found to have engaged in any scientific or ethical misconduct concerning any of his work."

[18] He told Oncology News International that he was “really very pleased and satisfied that the litigation is over and that I’m able to get back to doing my research under favorable circumstances.”[19] After the Poisson scandal was put to rest and Fisher's reputation restored, Fisher again took up his position at the NSABP, where he resumed his efforts to establish the efficacy of tamoxifen in lowering breast cancer risk in high-risk women.

[12] Fisher said that the greatest contribution of his career "was carrying out laboratory investigations...which have altered our understanding and treatment of breast cancer".

[11] The Atlantic magazine observed, "Today, medicine relies almost exclusively on randomized controlled trials and their more sophisticated cousins, meta-analyses, to guide treatment decisions.

[6] As remarkable as Fisher's scientific contributions, one colleague has written, "is that some 60 years into his career as a surgeon scientist he remains actively involved not just with accepting awards (which alone would keep him busy) but with adding to his bibliography of over 600 papers and with continuing to analyze and review the broad implications of his studies in the treatment of human disease".

[5] Fisher won the Albert Lasker Clinical Medical Research Award for 1985, which was given in recognition of "his profound influence in shaping the character of modern breast cancer treatment, thus lengthening and enriching the lives of women suffering from this dread disease".

The citation noted that Fisher had "done more than any other single individual to advance the understanding of the clinical biology of breast cancer" and "conceptually reshaped and improved the treatment of breast cancer, extending and enriching the lives of women suffering from this dread disease....From 1972 to 1981, the use of radical mastectomies has declined progressively from 46.8 percent to 4.5 percent.