The cessation of menstrual periods (amenorrhea) is common among premenopausal breast cancer patients undergoing chemotherapy. Younger women and women who started menstruating before age 13 are the least likely to experience chemotherapy-induced amenorrhea. Several studies have concluded that women whose menstrual periods persist throughout chemotherapy or resume quickly after stopping for a few months have a poorer prognosis than women who experience permanent chemotherapy-induced amenorrhea. Now a new study has reported that the absense of such amenorrhea predicts a poorer outcome even after taking age into account.

Periods stop for majority of premenopausal women on chemotherapy

At least 70% of premenopausal women who are treated with chemotherapy for breast cancer find that their menstrual periods stop by the end of chemotherapy. This change is permanent for a large minority. Cessation of periods has been observed for a wide variety of chemotherapy drugs and regimens, including those incorporating Adriamycin (doxorubicin), cyclophosphamide, Taxol (paclitaxel), and Taxotere (docetaxel), methotrexate, and 5-fluorouracil (5-FU). tamoxifen use appears to increase the length of amenorrhea or make it permanent.

One study reported that 70% of study participants experienced chemotherapy-induced amenorrhea: 41% of the women experienced six months of amenorrhea and 29% experienced at least one year of amenorrhea. Approximately half of the women with six months of amenorrhea and 29% of those with one year of amenorrhea resumed having periods within the following three years (usually during in first year after the end of chemotherapy). Of the 23% of women who experienced an initial two-year period of amenorrhea, 10% resumed having periods within the following three years, but none had regular periods.

Which women experience amenorrhea because of chemotherapy?

Efforts to determine which chemotherapy regimens are more likely to result in amenorrhea have not been especially successful; all of the modern regimens appear to cause the loss of periods. The determining factor appears to be the age of a woman Ś younger women are less likely to experience the loss of periods (and the associated loss of fertility).

One study reported that 76% of premenopausal women treated with an anthracycline and 83% of women treated with an anthracycline plus a taxane experienced amenorrhea. Chemotherapy-induced amenorrhea occurred in 95% of patients older than 45 years, while the proportion was only 52% in women under 40. Age was found to be the main predictive factor for chemotherapy-induced amenorrhea in both chemotherapy groups.

Another study that was designed to determine the association between patient characteristics(including age at first period, number of children, age at first birth, alcohol use, smoking history, and BMI and chemotherapy-related amenorrhea lasting at least six months reported that women who were over 13 years of age at first period were more than twice as likely to experience lasting amenorrhea as women who were younger at first period.

Prognosis is worse for women whose periods return

While a permanent loss of fertility as a result of chemotherapy can be devastating for young women with breast cancer, for most women, lasting chemotherapy-induced amenorrhea can be considered good news because it is a positive prognostic indicator. Several studies have reported that such amenorrhea is associated with improved survival among premenopausal women with breast cancer:

  • A study of 5,351 patients with lymph node-positive, early-stage breast cancer reported that overall survival was improved in patients with at least six months of amenorrhea, independent of estrogen receptor (ER) status.
  • A Canadian study of women with hormone receptor positive disease reported that six-month amenorrhea rates were not associated with prognosis. On the other hand, amenorrhea that continued for at least a year was found to be associated with approximately half the breast cancer recurrence rate of comparable women who continued to have menstrual periods.
  • A French and Belgian study reported that the incidence of chemotherapy-induced amenorrhea as of the end of chemotherapy was approximately 93%. A significant advantage in disease-free survival was found for patients who were still without periods after one year, compared to patients who had recovered regular periods.

Latest research reports new evidence concerning loss of periods

The study referenced at the beginning of this news article was designed to investigate the prognostic implications of the resumption or persistence of menstruation after chemotherapy for early-stage breast cancer. To conduct the study, the authors reviewed the existing medical records of 872 premenopausal women who received cytotoxic chemotherapy for stage I to III breast cancer. Study participants had a median age of 41 (range: 21 to 54 years) at diagnosis and were followed for a median of 6.2 years. A total of 692 (79.4%) of the participants had hormone receptor positive disease and most of these women were treated with tamoxifen after finishing chemotherapy. A total of 669 (76.7%) study participants experienced the cessation of menstrual periods as a result of chemotherapy and 452 (51.8%) had menstrual periods after chemotherapy during the follow-up period. A total of 121 (13.9%) of the women had persistent menstruation, without any interruption as a result of chemotherapy.

Disease-free survival was found to influenced by younger age at diagnosis (≤35 years), tumor size >2 cm, positive lymph nodes, hormone receptor negative disease, HER2 overexpressing disease (HER2+), and menstruation after chemotherapy based on single variable analysis. Using multivariate analysis, hormone receptor negative disease, tumor size >2 cm, positive lymph nodes, and menstruation after chemotherapy remained significant independent predictors for breast cancer relapse. The authors conclude that a considerable proportion of premenopausal patients treated with chemotherapy experience menstruation after chemotherapy-induced amenorrhea. Menstruation after chemotherapy is a poor prognostic factor for disease-free survival in premenopausal patients with early breast cancer.

Please see our article on the latest research on breast cancer in young women for more information.