The Breast Surgeon’s Perspective.
Cancer spreads mainly via the lymph system. The most likely route of spread for breast cancer is to the lymph glands in the armpit on the same side. Cancer itself does not often cause Lymphoedema because lymph can still pass through lymph glands containing cancer. Therefore Lymphoedema is not usually a presenting feature of cancer unless it is already advanced in its spread. However recurrence of cancer can trigger Lymphoedema and should always be considered in anybody who develops swelling after curative cancer treatment.
It is the cancer treatment that mainly produces the Lymphoedema. Current breast cancer treatment requires lymph glands to be removed in order to find out if the cancer has spread to them or not. Lymphoedema of the arm can develop when lymph glands are removed from the armpit. The more lymph glands removed the greater the risk of lymphedema.
Why are lymph glands removed?
Lymph glands are a collection point for cells leaving the tissues. This includes cancer cells, which, if gathered in sufficient numbers, will reproduce rapidly and set up camp within the lymph glands, so forming a metastasis. Metastasis means removal from one site to another (so cancer cells forming in the breast move to another body site e.g. lymph gland, where they ‘seed’ and start to grow to form a secondary tumor or metastasis).
Years ago it was customary to remove most, if not all, of the lymph glands in the armpit as curative treatment for breast cancer. Nowadays, selective and accurate sampling of the regional lymph glands, called the sentinel node biopsy, has completely replaced the complete removal of these glands in most women. It is only the women who have obvious spread of cancer to the glands in the armpit, either on feeling for lymph glands on clinical examination, or through ultrasound imaging of the glands, who do not undergo a sentinel lymph node biopsy.
Sentinel lymph node biopsy
The sentinel lymph node is the first lymph gland in the armpit to which cancer spreads. There may be more than one. The lymph glands are in a chain with lymph generally passing from one gland to the next. If lymph passes in succession from one gland to the next then so do cancer cells as they attempt to spread through the body. It is accepted that if the sentinel gland is free of cancer then the other glands in the armpit are likely to be as well, in which case there is no need to remove them.
To locate this lymph gland a dye is injected into the breast and followed until it reaches the lymph glands. The first lymph gland to absorb the dye is the sentinel lymph node (gland). The sentinel lymph gland is identified and removed. If there are two or even three sentinel lymph glands they are all removed. These glands can be examined in the laboratory while the patient is still under anaesthetic. If cancer cells are discovered under the microscope then the surgeon can go back and remove all the remaining lymph glands in the armpit.
Recent clinical trials conducted in the United States have demonstrated that complete removal of the lymph glands can be safely omitted in a significant proportion of women who have cancer spread to 1 or 2 (sentinel) lymph nodes only. This applies to women who undergo lumpectomy for breast cancer, and require postoperative radiotherapy to the breast and lower part of the armpit. This approach has become accepted as part of the national guidelines in the United States, but the vast majority of surgeons in the UK and Europe have not embraced it.
Women undergoing lumpectomy and sentinel node biopsy for breast cancer who are found to have cancer spread to only the sentinel lymph glands, should consider the option of not having further surgery. An alternative to more radical surgery i.e. removal of all remaining lymph glands in the armpit (known as an axillary clearance), is radiotherapy to the armpit.
Radiotherapy
The scientific evidence clearly demonstrates that the more extensive the surgery in the armpit, the higher the risk of Lymphoedema. However, radiotherapy to the lymph gland areas is not without risk. Although the armpit is the main route for spread of breast cancer cells, the lymph glands above the collarbone can be involved. These glands are not surgically sampled or removed but are usually treated with radiotherapy.
Many of us remember the effects of super doses of radiotherapy that were used in the 1980s in an attempt to cure breast cancer through radiation. Such was the severity of the long-term side effects, including arm Lymphoedema, that questions were asked in the British Parliament. The patient advocacy group RAGE, the Radiation Action Group Exposure, campaigned for quality assurance in radiotherapy, and succeeded in getting the problem recognized and so improve patient care.
Surgery has a short-term damage effect, and recovery is probably complete after 18 months, whereas radiotherapy has a detrimental effect for many years to come. Therefore we may not know for a long time if the use of radiotherapy to the armpit, instead of radical surgery, will reduce the incidence of arm Lymphoedema or not.
Chemotherapy
There was a time when chemotherapy was considered irrelevant for Lymphoedema risk but not any more. Recent evidence suggests that those patients treated with taxanes have a significantly higher risk of developing Lymphoedema. Taxanes are derived from plant alkaloids and work by blocking cell growth (the defining feature of a cancer cell is fast reproduction). Examples are paclitaxel (Taxol) and docetaxel (Taxotere). We will address how and why Lymphoedema develops after breast cancer treatment later, but taxanes are likely to increase the fluid load by making blood vessels in the arm release more fluid. This extra fluid load will overwhelm lymph drainage already weakened by lymph gland removal.
Breast Lymphoedema
With the advent of minimalist surgery for breast cancer treatment so the problem of breast Lymphoedema has emerged. In the days of mastectomy, when the whole breast was removed, breast edema was clearly not a problem. Standard treatment now is for a ‘lumpectomy’ or wide local excision so conserving the breast. That increases the chances of local recurrence of breast cancer, so, to overcome this, radiotherapy to the breast is administered.
Radiotherapy has an effect like sunburn and causes inflammation of the breast and overlying skin. This causes fluid to build up in the breast because the lymph drainage does not work properly. Lymph drainage from the breast occurs for two reasons: first, lymph drainage from the whole breast is compromised to some extent following the removal of one or more lymph glands from the armpit; and second, the local lymph vessels in the skin of the breast suffer directly from the radiation and lymph flow through them is reduced.
Edema of the breast that persists after the ‘sunburn’ effect of the radiotherapy has subsided is Lymphoedema. Lymphoedema of the conserved breast has received much less attention than swelling of the arm. Breast Lymphoedema is uncomfortable at best, and painful at worst. Furthermore it leads to a lopsided cosmetic effect, which may be difficult to hide under clothing if the swelling is severe. Another problem that can arise is cellulitis of the breast because of the compromised lymph drainage and the consequent reduction in immunity within the breast tissues. The good news is that if infection can be prevented and treatment pursued the breast Lymphoedema can eventually resolve.
Weight gain and cancer treatment
Steroids are commonly given with chemotherapy in order to reduce side effects. Steroids often cause weight gain, which is a risk factor for lymphedema. Weight gained through steroids may persist long after the steroids have finished and may prove difficult to lose.
Hormonal therapy is often given long term (5-10 years) to discourage return of the breast cancer. Certain breast cancers are hormone sensitive. This means that hormones, such as estrogen and progesterone, promote the growth of the cancer. By blocking these hormones so the regrowth (relapse) of the cancer can be prevented. One of the side effects of blocking estrogen is weight gain.
Research has shown that being overweight is one of the strongest risk factors for Breast Cancer related Lymphoedema. While the priority is to cure the cancer it is unacceptable to many patients if the cost is obesity and Lymphoedema.
Breast reconstruction
The negative impact of lymphedema negates a positive impact achieved by breast reconstruction in women who have mastectomy and reconstruction. Women undergoing mastectomy for breast cancer should be aware that immediate breast reconstruction does not appear to increase the risk of lymphedema. In fact, there is anecdotal evidence that it may reduce its incidence compared to having mastectomy without reconstruction. We also don’t know if reconstruction in those women who already have lymphedema makes it worse.
Who gets breast cancer related lymphedema?
Breast Cancer related Lymphoedema still remains much of an enigma with regard to who gets it. Why the majority of women who have all the lymph glands removed from their armpit do not get swelling, yet 6% of women who have only one lymph gland removed get arm swelling, is not known. Why some women get Lymphoedema immediately after their surgery, some after chemotherapy and radiation, and others not for many months or years is not known. Why some women get hand swelling yet others do not, despite swelling of the forearm, is not known.
The evidence is that the main risks for the development of Breast cancer related Lymphoedema are a) the extent of the surgery and, in particular, having more lymph glands removed, b) radiotherapy and especially treatment of the armpit, and c) being overweight; the greater the weight the greater the risk.
Another risk factor that is probably important but less clear-cut is infection, because infection immediately after surgery adds further insult to lymph drainage routes.
How does lymphedema occur?
It is assumed that it is obstruction to lymph flow in the armpit from the surgery as well as the radiotherapy that leads to arm swelling. However recent research suggests the mechanism is far more complicated.
As explained previously any edema results from a mismatch between fluid entering the arm and fluid leaving the arm. If more fluid enters than leaves then swelling (edema) will occur. The fluid enters via the blood vessels and leaves via the lymph vessels. Because the lymph vessels all leave at one point in the armpit, obstruction there would be like a stopcock. However a tightening of a stopcock would result in a build up of fluid in the entire arm including the hand and this is not what generally happens. As said earlier the hand is frequently spared.
The analogy would be damming a river so that upstream water can no longer pass down the main channel and consequently has to take an alternative route, either via existing streams or by forging new rivers. If water cannot escape then flooding occurs.
The recent scientific evidence points to an inborn, and probably genetic, predisposition to Lymphoedema. In studies of breast cancer patients investigated from the time of diagnosis and followed for 3 years after they have completed cancer treatment, changes in physiology have been found even before the first surgery. Higher levels of lymph drainage have been found before surgery in the arms of those women who goes on to develop Lymphoedema than in those women who never develop Lymphoedema. The lymph vessels appear to be working harder. These events can only be explained because fluid turnover in the arm is higher. Indeed higher fluid turnover has been measured in both arms hence why a constitutional or inborn predisposition has been suggested as the explanation.
In summary while surgery to the armpit does compromise lymph drainage from the entire arm, Lymphoedema only develops in those women who have lymph vessels which are already working hard because of high fluid demands determined by an inborn difference in their physiology. These hard working lymph vessels fail when they have to work even harder because of the removal of one or more lymph glands
