BREAST CANCER

INCIDENCE

By Daniel A Vorobiof, Freddy Sitas, and Gabriel Vorobiof

Abstracts:  Cancer in South Africa is an emerging health problem, with breast cancer being one of the leading cancers in women, following similar world­wide statistics. Lifetime risks of developing breast cancer vary from a low of one in 81 in African women (similar to Japan) to a high of one in 13 among white women, similar to rates in Western countries. Age and stage at diagnosis vary considerably between the dif­ferent races and populations (urban v rural) living in South Africa. Many different determinants (socioeco­nomic, cultural, geographic accessibility to medical centres with oncology services, availability of traditional healers, and so on) affect patients with breast cancer (mainly rural black women) in their decisions to obtain early medical help as well as to refrain from the proposed therapeutic methods (surgery, radiotherapy, and chemotherapy).  A brief overview of breast cancer in South Africa with special reference to some of the above determinants is presented.

J Clin Oncol 19:125s – 127s. © 2001 by American Society of Clinical Oncology.

SOUTH AFRICA IS A diverse country of 1.2 million square km and of about 40 million people divided into 31 million of black/African origin, 5.2 million of white origin, 3,5 million of mixed race origin, and 1 million of Asian/Indian origin, approximately 25% to 30% of the population live in urban areas. Eleven official languages are recognized, with English being the most commonly used.

In South Africa, one of the sources of information on cancer morbidity is the National Cancer Registry, which collects all information of cancer diagnosed from all of the country’s pathology laboratories.  As a result, this is an underestimate of the true incidence of cancer.

Nevertheless, in females cancer of the breast has been the second leading cancer between 1986 and 1992 (cervical being the leading cancer), but between 1993 and 1995, it seems to have overtaken cervical cancer, and it is now the most common cancer in women (16.6%). It ranked the most common cancer in white (17.9%) and Asian (24.4%) women and the second most common cancer in mixed­ race (18.2%) and black (13.4%) women.  It is unclear whether this  between cervical and breast cancer is real or whether it has been as a result of a reduced number of tests done, for example, for cervical cancer in the public sector hospitals, as a result of budget con­straints. Between 1993 and 1995, an annual average of 3,785 new cases of breast Cancer were reported by the National Cancer Registry versus 1,572 deaths reported to Statistic South Africa in 1994. During the same years, the crude incidence rate was 18.5 per 100,000, and the age-standardized incidence rate was 25.1 per 100,000. The lifetime risk (0 to 74 years) was one in 36 overall but varied from one in 81 in black to one in 13 white women, a six-fold difference. In mixed-race and Asian women (mainly of Indian origin), the lifetime risk was   

Breast Cancer Types

  1. A) INVASIVE BR CA                                  

1.Infiltrating Ductal carcinoma (invasive ductal carcinoma)

Most common breast carcinoma (-75%)

Characterized by stony hardness on palpation.

Gritty resistance encountered upon transect ion; used to be called “scirrhous” carcinoma.

Typically metastasizes to bone, lung and liver.

  1. Tubular carcinoma

It is a variant of infiltrating ductal carcinoma.

Often detected by mammography.

-5% of all breast cancer

Better prognosis than infiltrating ductal carcinoma.

Can be difficult to distinguish from radial scar (benign proliferative lesion).

Typically ER ( +) and progesterone receptor (PR) (+).

  1. Medullary carcinoma

5-7% of all breast cancer.

Females tend to be younger at diagnosis (< 50 years old). .

Better prognosis than usual infiltrating ductal carcinoma. Must have all the above features for better prognosis:

  1. Mucinous or colloid carcinoma
  • ~ 3% of all breast cancer.
  • Characterized by abundant accumulation of extracellular mucin around clusters of tumour cells.
  • It is slow growing and can become bulky.
  1. Papillary carcinoma
  • ~ 1-2% of all breast cancer.
  • Tends to occur in older females.
  • Mostly a variant of an in situ cancer
  • Good prognosis.
  1. Infiltrating lobular carcinoma
  • ~ 5-10% of breast cancer.
  • Subtypes: solid, alveolar, pleomorphic (poor prognosis).
  • Characterized by ill-defined thickening or induration in the breast:

o    can be difficult to identify grossly

o    frequently presents in the upper outer quadrant.

  • Greater proportion of multicentric tumours, either in the same or opposite breast, compared with infiltrating ductal carcinoma.

The following types of invasive breast cancer – pure colloid, tubular, papillary, medullary – are commonly felt to have a lower incidence of nodal involvement and a better prognosis for any given tumour size.

Other rare carcinomas include: apocrine, squamous cell carcinoma, spindle cell carcinoma, carcinosarcoma, Merkle-cell carcinoma, and adenoid cystic carcinoma.

  • Paget disease
  • Intraepidermal adenocarcinoma of the nipple. Neoplastic eczematoid changes around the nipple. Clinically appears as a rash on the nipple.
  • Almost always associated with underlying ductal carcinoma, usually DCIS.

Inflammatory breast cancer

[Hortobagyi GN, Treatment of locally advanced and inflammatory breast cancer. In: Harris JR, et al (eds), Diseases of the Breast, 2nd edn. Lippincott, Williams & Wilkins, Philadelphia, 1999, l’ 650]

  • Most aggressive.
  • ~ 1-3% of breast cancer newly diagnosed in the USA.
  • ~ 25% of these patients have breast or nipple pain.
  • Rapid onset.
  1. B) Ductal carcinoma in situ (DCIS) Intraductal neoplasia is the new name.
  2. C) Lobular carcinoma in situ (LCIS)

Both B and C are cancers confined to the ducts and lobules and are as such not real cancers, not being able to spread to other sites.

They have the potential to develop into invasive cancers over years, but not all of these do that.

They often present on a mammogram as micro calcifications.

More than 40% of breast neoplasias detected on mammograms are of these types.

Being detected early before they become invasive(real) cancers,,mammography contributed the major part in reduction of breast cancer mortality over the last 30 years.

They are not detected on ultrasound, and therefore, US should not be used as sole screening method in women over 40yrs.

As they are not real cancers and not able to metastasize, they should be treated conservatively.

To complicate matters and management, they often appear in the neighbourhood of invasive cancers and this characteristic then often lead to more aggressive surgery offered to women.

BREAST CANCER TREATMENT

Because there are many variables and many types of breast cancer, treatment must be tailored for every individual women and type. Treatment should be planned in a multidisciplinary setting with all the role-players present. That mean radiologist to give information about size, extent and position of the tumour. The surgeon, to give opinion about the feasibility of a procedure and technical pitfalls. The oncologist to plan treatment before or after surgery. Often the reconstructive surgeon opinion and planning is also needed before-hand. The treatment plan and schedule should be explained to the women and her spouse and all her questions be answered. She should then be given ample time to consider the proposals and if requested obtain more opinions and information from international renowned centres.

Treatment could be the following and timing schedule could vary according to each case:

Surgery: The goal must be to conserve the breast as there is no proven survival benefit for mastectomy over lumpectomy. SEE TRIALS

post tattoo lumpectomy

Post lumpectomy

If the cancer mass is too big or breast volume too small, the option to shrink the tumour with primary systemic treatment (PST) should be considered. This often downstages the tumour to a more manageable size.

Mastectomy is sometimes unavoidable but should be offered as a last option.

It should be enough to excise the tumour (LUMPECTOMY) with clear margins even if more than one tumour is present in the same quadrant of the breast. The more experienced the surgeon, the better cosmetic result could be obtained and the less likely he/she will opt for mastectomy.

The way forward: Breast cancer surgery

Alberta Costa

Director, Breast Surgery Unit, Fondazione Salvatore Maugeri, Pavia and Director, European School of Oncology, Milan, Italy

I have dedicated my entire professional life to the field of breast cancer, an experience which has transformed me. I have operated on more than 3000 women. While I do not remember all of them, they all have left something in my mind, in my heart, in my experience of life.

I started to study medicine because I was attracted by science. Science is based on curiosity, and doubt. This is an important aspect that scientists and advocates share. Advocates should always doubt, not trust, and should always ask why and if it can be done another way. History of medicine indi­cates at there are very few dogmas which resist over the years. Over the last 30 years, what we have done in breast Cancer has been a constant challenge to our dogmas. My men­tor, Umberto Veronesi, did this in 1973, when we accepted the first volunteers willing to be randomised to have breast-conserving sur­gery instead of mastectomy. I was very lucky to be in the right place at the right time. I will never forget those women in 1973 that were diagnosed with breast cancer but did not have a mastectomy. It was something extraor­dinary, very challenging and dangerous.  However, now we know that mastectomy was a dogma and that it was correct to challenge it. Today, the future of breast cancer patients does not depend on how much of the breast is removed, but on other factors as explained below.

In both advocacy and science, there is a strong need to constantly re-discuss and reconsider. This is a duty. There is also the dogma of axilliary resection and the need to remove all the lymph nodes. This is not nec­essary now as the sentinel node biopsy is an effective procedure. There is also the dogma of full radiotherapy, among others.   ‘

There is a paradoxical situation: breast can­cer is increasing in incidence worldwide, even in countries where it is relatively low, such as India, Vietnam, Korea, Thailand, China and Gambia, yet mortality is declining in many Western countries, reflecting increased awareness, early detection and better treat­ment. It is hypothesised that the increased incidence is due to changing lifestyles. Throughout the ages, women had children starting at a young age and breastfed them for a year or longer. Now the average age for the first pregnancy in Western Europe is 26. Women have only one or two pregnancies and breastfeed for an average of 3 months. Such an important change in the biology and in the nature of the breast, glands and cells will have consequences. It is believed that this is the reason for the increasing incidence of breast cancer; it is increasing in all the regions where these changes are occurring. On the other hand, thanks to screening, early diag­nosis, awareness and treatment, mortality has been constantly decreasing over the last 5 years. Nonetheless, unfortunately too many women die of breast cancer, not because of the biology of the disease, but because the disease was not diagnosed early enough or it was not treated properly. This is a challenge for doctors, advocates and politicians.

Changing treatment concepts

Most of the changes in breast cancer treat­ment have occurred in the last 30 years. It has been a Copernican revolution, with the most important concept being the switch from maximum tolerated treatment in 1970 to minimum effective treatment in 200Q. From 1894, when Halstead developed the mastec­tomy, until almost 1970, the only treatment was mastectomy. In 1962 researchers in Paris suggested that in addition to removing the breast and the lymph nodes, other lymph nodes should be resected because the cancer cells can spread to the axilla, the internal mammary lymph nodes near the sternum and to the supraclavicular lymph nodes. This pro­cedure was known as the enlarged mastectomy.

MODERN BREAST CANCER SURGERY

The above is a summary of what changed in the past 30 years. We have moved from the most radical and mutilating radical mastectomy to tailored breast conserving procedures like lumpectomy and segmentectomy. We even do procedures to remove the nipple areola complex and still save the rest of the breast. It is always best to have your own breast even if the nipple must be removed and reconstructed later on.

It is very important for all women challenged with surgical decisions, to consider the following facts before making a decision to have a mastectomy or not:

  • Radical surgery like mastectomy, has no survival benefit compared to lumpectomy plus radiation. Many trial since 1973 have proven that. Look under MORE INFO AND TRIALS. These trials comparing the survival of women who had mastectomy versus women who had lumpectomy plus radiation, now run for 30 yrs and still there is no difference in the survival between the 2 groups.
  • Thus, the more radical surgery does not mean longer survival. She should question her surgeon about this and go through the trials to understand that,
  • The long term psychological effects of losing her breast are serious. She should not think it will not harm her body image. The husband and the women often find it difficult to adapt, with serious effects on their sex life and spontaneity.
  • There are methods to treat the cancer before surgery in order to reduce tumour size, to increase the likelihood of saving her breast. This can be done with hormone manipulation (anti-estrogens) or chemotherapy. This PST (primary systemic treatment) has been proven by many trials to be safe and not to influence survival endpoints. See under PST topic. In many instances PST could have great advantages.
  • In fact, the are certain types of breast cancer that do worse if operated first,  before PST(the Her-neu oncogene positive types)
  • A good breast surgeon is one that can save a breast with good cosmesis. A mastectomy is easy surgery.
  • Like mastectomy in the past was a dogma, it is the same with total lymph node dissection (removal) in the axilla. It should always be our aim to save the nodes in the axilla, with techniques like sentinel lymph node mapping (SLN mapping) Removal if the glands in the axilla carries a considerable morbidity for the rest of the woman’s life (swelling and pain in the arm and recurrent infections) The women should enquire about SLN as not all hospitals have the equipment and expertise to do that.
  • Minimal required surgery should be done, as the surgery on the breast is mainly for local control and has little influence on survival.
  • A reconstructed breast can never compare with her own breast albeit smaller.

To do mastectomy of the normal, other breast, does not make sense. It is usually the first cancer that has spread and causes death and not a possible second one developing years later.

We do not even remove a breast with cancer anymore….. Why would we sacrify a breast without disease??

Mastectomy vs. breast-conserving therapy (BCT)

  • [Keynes G, BM] 2: 643-647, 1937]

– Dr Geoffrey Keynes, a surgeon at St Bartholomew’s Hospital, London, began treating operative breast cancer patients conserva­tively in 1924.

  • Local excision with radiotherapy produces equivalent results, in terms of survival, when compared to mastectomy.
    • Proven by seven randomized trials.
    • [NCI Consensus Conference,]AMA 265: 391-3951,1991]

CONCLUSION:

Breast-conserving treatment is an appropriate primary therapy for the majority of females with stage I/II breast cancer.

  • Lumpectomy with level I and II ALND + XRT= total mastectomy +ALND:

– If tumour T < 4 cm

– And clear margins.  

Table 14.1              Breast-conserving therapy:  Randomized trials

Institution Years No of patients Overall survival (%)
Milan (1) 1973 – 1980 349 (M)352 (Q + XRT) Same (20 years)
NSABP-B06 (2) 1976 – 1984 590 (M)629 (L + XRT) Same (20 years)
Danish Breast Cancer Cooperative Group (BCG) (3) 1983 – 1987 429 (M)430 (L + XRT) 82 (6 years)79
Institute Gustave-Roussy Breast Cancer Group (4) 1972 – 1979 91 (M)88 (L + XRT) 65 (15 years)73
NCI (5, 6) 1980 – 1986 116 (M)121 (L + XRT) 75 (10 years)77
EORTC 10801 (7) 1980 – 1986 426 (M)456 (L + XRT) 63 (8 years)58
Guy’s Hospital (8) 1981 – 1986 185 (M)214 (L + XRT) Equal(54 months)

 

*M, mastectomy; L, lumpectomy; Q, quadrantectomy; XRT, radiation therapy. All females underwent ALND.

1 (Veronesi U, New Eng/ J Med 347: 1227-1232, 2002)

2 (Fisher B, N Engl J Med 347: 1233-1241, 2002)

3 (Blichert-Toft MJ, Nat/ Cancer Inst Monograph 11: 19-25, 1992)

4 (Arriagada R, J Clin Oncol 14: 1 558-1 564, 1 996)

5 (Lichter AS, J Clin Onco/1 0: 976-983, 1992)

6 (Jacobson JA, N Engl J Med 332: 907-911, 1995)

7 (vanDongen JA, J Natl Cancer Inst Monograph 11: 15-18, 1992)

8 (Chaudry MA, Breast Cancer Res Treat 14: 140, 1989)

  • Currently there is no consensus regarding the optimal extent of sur­gery required (lumpectomy vs. quadrantectomy) before irradiation.

– The approach is influenced by the size of the area to be resected in relation to the size of the patient’s breast.

  • [Early Breast Cancer Trialists Collaborative Group (EBCTCG), N Engl J Med 333: 1444-1455, 1995]
  • Overview (meta-analysis) of randomized trials of local therapies for early breast cancer looks at effects on mortality and local recurrence.

LONGTERM SURVIVAL OF MASTECTOMY VS LUMPECTOMY OVER 20 YRS

Graph

survival rate

 

Sentinel lymph node mapping.

This procedure should now be offered to all women. There are many trials to prove its safety and ability to prevent total removal of normal axilliary glands. SEE TRIALS.

The procedure is planned the day before the surgery and is done in the Nuclear Medicine department and completed during the lumpectomy in theatre.

Radiation

To equal mastectomy survival rates, the breast must be radiated after lumpectomy. The total dose delivered to the breast is fragmented over 6 weeks. It result in sterilisation of the rest of the breast, and lowers the recurrence rate in years to come. As mastectomy, whole breast radiation was also a dogma which will be replaced by accelerated partial breast radiation with equal results. SEE Alberta Costa comment on this. (Under BREAST SURGERY THE WAY FOREWARD) APBR is already used with success in Europe and the US but in SA, it is still under a cloud of scepticism, mainly from the side of medical funding and hesitance of radiation oncologists. This procedure which entails placing of a radiation delivery balloon inside the lumpectomy cavity could save women a lot of inconvenience and could prevent women from not attending for radiation. Cosmetic results are also far superior to whole breast radiation.

Primary Systemic Treatment (PST)

case study 7

With this approach, the tumour size is reduced before surgery, resulting in a smaller volume of breast be reduced. The oncologist and surgeon should have the intimate involvement of the onco-radiologist to do this with confidence and safely. SEE our technique of tattooing the shrinking tumour with activated carbon to assist with future removal of the remaining tumor. SEE ACTIVATED CARBON TATOO elsewhere.

As you will read under TREATMENT, we strive to save a woman’s breast, as many trials failed to show any survival benefit of mastectomy over lumpectomy (breast conservation-removal of the tumour only).

Tumours too big to be removed and still leave a good cosmetic result, can be treated pre-operatively to make them smaller. It enables us to remove a smaller portion of tissue and leaves the patient with a better breast volume and cosmetic result.

Depending on the histology of the tumour, obtained from a core needle biopsy, the tumour is first treated systemically with either chemotherapy or hormonal manipulation (in future perhaps also by local kryo therapy), and then removed.

Advantages of treating first and then surgery.

1) The effect of the treatment can be judged, and measured, in the breast by measuring the shrinking size of the tumour using ultrasound, mammography, or MRI.  If it does not shrink, you know your treatment protocol is ineffective and should be changed. When surgery removes the tumour first, you never know if your treatment is having an effect. We thus have a measurable tool.

2) Treatment can be started immediately (systemically).  When surgery is done first; one has to wait (+- 6 weeks) for the wounds to heal before you can start chemotherapy.

3) When the tumour is smaller, the surgeon needs to remove a smaller portion of the breast. This also downstages your type of surgery and a mastectomy can often be avoided. Less aggressive surgery of the axilla follows.

4) Many trials (see TRIALS) show that the survival rate in PST patients is not compromised, compared to surgery first. In actual fact, there are certain types of Breast Cancer (Her-neu positive) that have worse prognoses when operated on first, before PST.

5) It must always be kept in mind that it is the systemic spreading of the cancer that kills, and not the tumour in the breast. The sooner the cancer seeds in the body are treated, the better.

Trials to support this approach and that it is safe, can be read under TRIAL AND MORE INFO.

Chemotherapy

The cancer and rest of the body is treated with chemicals to kill of cancer cells in the breast and rest of the body tissues. This can be done before surgery (PST) or after surgery. (ADJUVANT)The type of pharmaceuticals used in combination varies according to the type of cancer, and results found to be effective in trials.

Hormonal Manipulation

Anti-estrogens are used to treat before or after surgery. These include well known agents like Tamoxifen and aromatase inhibitors. There job is to block the growth stimulation effects of circulating estrogens in the woman’s body. This is effective in cancers which are Estrogen receptor positive. About 72% or more of breast cancers are now found to be Er.positive.

These anti-estrogens are today a valuable new weapon in our treatment armentarium. In young women with ovarian function, the function of the ovaries can also be knocked out by chemicals instead of removing the ovaries surgically.

Monoclonal Antibodies

In aggressive types of cancer where we found a certain oncogene (Her-neu) to be present, a drug like Herceptin is used to suppress cancer growth. This reduces mortality significantly.

THE BOTTOMLINE IN TREATMENT IS: All women should be treated according to her specific cancer type and there is no universal treatment for all cancers like believed in the past.

Other methods of treatment are under investigation.

Radio Frequency ablation and Kryo ablation of the tumour bulk are being investigated in larger research centres and hold promise. This could mean that surgery for breast cancer might further be scaled down in future.