Menstrual Cycle Patterns and Breast Cancer

The breast tissue in females undergoes cyclical changes in its structure, protein expression and cellular functions, which correspond with the different phases of the menstrual cycle. These normal cyclical changes in the breast tissue are however, disturbed in women suffering from breast cancer due to a process called as “global dysregulation of response to hormonal influences.”In this process, the cancer cells do not respond in a normal fashion to the difference in hormonal levels, during the various phases of the menstrual cycle.
 

On the basis of the influence of the different sex hormones, namely estrogen, progesterone, luteal hormone and follicular stimulating hormone, the menstrual cycle has been classified into four stages. They are:

• Early Follicular Stage

It is also called as stage 1 and corresponds to day 0 to day 5 of the menstrual cycle.

• Late Follicular Stage

It is also called as stage II and corresponds to day 6 to day 15 of the menstrual cycle.

• Early Luteal Phase

It is also called as stage III and corresponds to day 16 to day 24 of the menstrual cycle.

• Late Luteal Phase

It is also called as stage IV and corresponds to day 25 to day 28 of the menstrual cycle.

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Classification of breast changes corresponding to different phases of menstrual cycle

The menstrual phase of the breast tissue is assessed on the basis of the size of the breast lobules, character of the luminal cells, vacuolation in the myoepithelium, intraluminal secretion, intralobular stroma, mitosis and apoptosis. Depending on the stage of changes in these features, the cyclical changes of the breast tissue can be classified as:

• Phase of Regression

This phase lasts from day 1 to day 8 and is characterized by atrophy of myoepithelium, condensation of intralobular stroma, and presence of an inflammatory infiltrate.

•  Phase of Proliferation

This phase corresponds to the later half of the menstrual cycle. There is alveolar budding, secretions and stromal edema. Many apoptotic figures are seen towards the end of this phase.

Another commonly used method of classifying breast changes according to different phases of menstrual cycle is as follows:

• Proliferative phase
• Follicular phase of differentiation
• Luteal phase of differentiation
• Secretory phase
• Menstrual phase

Among these different phases of breast tissue changes, it is the late luteal phase which is of special interest to scientists studying the relationship of breast cancer with menstrual cycle. During this phase there a rapid proliferation of breast epithelial cells, because of a cumulative effect of both estrogen and progesterone. The breast lobules exhibit many apoptotic figures and there is an increased level of mitotic activity, which may lead to development of cancer in high risk individuals.

It is important to know about the changes that occur in the breast tissue because of two reasons:

1. It helps in matching patients according to the changes in their breast tissue corresponding to their menstrual cycle, for different epidemiological studies relating to breast cancer.
2. Certain studies have suggested that surgery for breast cancer, when performed in the luteal phase of the menstrual cycle, has a better prognosis.

Exposure to Increased Levels of Estrogen can Play an Important Role in the Development of Breast Cancer

The likelihood of a woman developing breast cancer is affected by her age at the time of commencement of her menstrual periods and at the time she attains menopause. Similarly, the age of the woman when she first gives birth to a child, has also been demonstrated as an important risk factor in the development of breast cancer in many epidemiological studies.
 
We all know that the endocrinal environment inside a woman’s body goes for a toss at the time of menarche, menopause and pregnancy. This hormonal upheaval in the three phases of reproductive life of a woman can play an important role in the pathogenesis of breast cancer.

An orderly cyclical pattern of follicular maturation, development of corpus luteum, and its regression associated with specific changes in he levels of different sex hormones leads to menstruation. Women are known to have irregular periods just after menarche and in the years prior to menopause. This occurs because of improper follicular maturation and the impaired corpus luteum can lead to insufficient production of progesterone. The hormonal environment thus produced due to a deficiency of progesterone, is rich in estrogen. Something similar happens in case of delayed menopause. Here again, a woman experiences irregular periods and the hormonal environment thus produced, is rich in estrogen. An involuntary infertility is often the cause of delayed age of first parity. Once again, it is the inadequate production of progesterone during the luteal phase of menstrual cycle which gives rise to involuntary infertility. A progesterone deficient environment means an increased exposure to estrogen.

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As all the three conditions, i.e. early age at menarche, late onset of menopause and a delayed first pregnancy have been associated with a high risk of development of breast cancer, one can infer that exposure to increased levels of estrogen in these conditions can play an important role in the development of breast cancer. Moreover, even if a woman has normal menstrual cycles, an early age at menarche and a delayed onset of menopause means that she experiences more number of menstrual cycles in her reproductive age. This means that she experiences a greater cumulative estrogen exposure. Studies have revealed that women who experience a greater (more than 350) cumulative number of menstrual cycles, have an increased incidence of breast cancer.

The menstrual cycle is also related to the treatment of breast cancer in women. Certain studies have shown that adjuvant surgical oophorectomy during the luteal phase of the menstrual cycle is better than removal of ovaries in the follicular phase. It results in reduced risk of recurrence of the breast cancer during the first 5.5 years of follow up. However, the benefits of luteal phase surgery on the chances of recurrence of breast cancer are not appreciable after 6 years of surgery.

There is still a lot of controversy regarding the benefits of luteal phase surgery for breast cancer as there are many other studies which do not support this view. A lot of work has to be carried out in this field before one can establish the ideal time of breast cancer surgery in relation to the different phases of menstruation.