The study, published in the British Journal of Cancer, followed over 50,000 postmenopausal women from five racial/ethnic groups and found that regular consumption of the fruit increased the risk of the cancer.
Every year, over one million women are diagnosed with breast cancer worldwide, with the highest incidences in the US and the Netherlands. China has the lowest incidence and mortality rate of the disease.
Both the researchers and independent experts have warned that the results should be treated with caution, with further research needed to further explore the association.
Grapefruit is being increasingly marketed for its healthfulness, with the fruit currently positioned as containing antioxidants, which may help prevent certain types of cancer, heart disease and stroke. Grapefruit also contains natural vitamin C and potassium.
The researchers, from the University of Southern California and the University of Hawaii, documented 1657 incident cases of breast cancer, and calculated that eating the most grapefruit, equivalent to about one-quarter of a full fruit everyday, were at a 30 percent increased risk of the disease.
"Grapefruit intake may increase the risk of breast cancer among postmenopausal women," they concluded.
Monroe and co-workers suggested that the link might come from an interruption of the action of cytochrome P450 3A4 (CYP3A4), which is involved in the metabolism of estrogens.
"There is evidence that grapefruit, an inhibitor of CYP3A4, increases plasma estrogen concentrations," said the researchers. "Since it is well established that estrogen is associated with breast cancer risk, it is plausible that regular intake of grapefruit would increase a woman's risk of breast cancer."
However, since this is reportedly the first time that a commonly consumed fruit has been linked to an increased risk of cancer and that significant further research is needed.
Commenting independently on the research, Joanne Lunn from the British Nutrition Foundation told the BBC: "This is an interesting study of a large group of post-menopausal women whose diet and health have been followed for many years.
"However, this study is simply a piece of the jigsaw that will eventually help us to understand how our diets affect our health.
"Although we are beginning to get a better awareness of how our diets can modify the risk of diseases such as cancer, we are still a long way from identifying particular foods that might specifically increase or decrease risk," she added.
Grapefruit harvest generally takes place between October and April, with around 40 percent of the grapefruit harvested each season being used for juice, while 60 percent are sold as fresh grapefruit.
According to Ocean Spray, a juice marketer owned by 650 cranberry growers and 100 Florida grapefruit growers, the grapefruit industry was nearly destroyed in recent years by a string of natural disasters.
In 2005, Florida, the world's largest grapefruit-growing region, was hit by back-to-back hurricanes and storms, which extensively damaged many grapefruit groves leading to a loss of production and higher costs for consumers.
But this year the industry is "making a comeback", according to Ocean Spray.
The group forecasts the Florida grapefruit harvest will almost double from 19 million boxes a year ago to 28 million this year.
Source: British Journal of Cancer Advance online publication, doi:10.1038/sj.bjc.6603880
"Prospective study of grapefruit intake and risk of breast cancer in postmenopausal women: the Multiethnic Cohort Study"
Authors: K.R Monroe, S.P. Murphy, L.N. Kolonel and M.C. Pike